255 results on '"Eychène, A"'
Search Results
2. Mafa-dependent GABAergic activity promotes mouse neonatal apneas
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Lecoin, Laure, Dempsey, Bowen, Garancher, Alexandra, Bourane, Steeve, Ruffault, Pierre-Louis, Morin-Surun, Marie-Pierre, Rocques, Nathalie, Goulding, Martyn, Eychène, Alain, Pouponnot, Celio, Fortin, Gilles, and Champagnat, Jean
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- 2022
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3. MITF activity is regulated by a direct interaction with RAF proteins in melanoma cells
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Estrada, Charlène, Mirabal-Ortega, Liliana, Méry, Laurence, Dingli, Florent, Besse, Laetitia, Messaoudi, Cedric, Loew, Damarys, Pouponnot, Celio, Bertolotto, Corine, Eychène, Alain, and Druillennec, Sabine
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- 2022
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4. MITF activity is regulated by a direct interaction with RAF proteins in melanoma cells
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Charlène Estrada, Liliana Mirabal-Ortega, Laurence Méry, Florent Dingli, Laetitia Besse, Cedric Messaoudi, Damarys Loew, Celio Pouponnot, Corine Bertolotto, Alain Eychène, and Sabine Druillennec
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Biology (General) ,QH301-705.5 - Abstract
The MITF transcription factor directly binds to the kinase domain of RAF kinases, including ARAF, BRAF and CRAF in melanoma cells. RAF/MITF complex promotes cytoplasmic accumulation of MITF and thus negatively regulates its transcriptional activity.
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- 2022
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5. The 5P program, personalized and participatory primary prevention pathway: Rational and design of a clinical trial in general practice
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Legrand, Florian, Eychene, Jean-Marc, Audiffren, Julien, Klein, Armelle, Labourdette, Christophe, Nicolaï, Alice, Sandron, Frédéric, and Vidal, Pierre-Paul
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- 2021
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6. In Vivo Medulloblastoma Modeling
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Mirabal-Ortega, Liliana, primary, Larcher, Magalie, additional, Morabito, Morgane, additional, Foray, Chloé, additional, Duvillié, Bertrand, additional, Eychène, Alain, additional, and Pouponnot, Celio, additional
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- 2020
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7. Translational control of tumor immune escape via the eIF4F–STAT1–PD-L1 axis in melanoma
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Cerezo, Michaël, Guemiri, Ramdane, Druillennec, Sabine, Girault, Isabelle, Malka-Mahieu, Hélène, Shen, Shensi, Allard, Delphine, Martineau, Sylvain, Welsch, Caroline, Agoussi, Sandrine, Estrada, Charlène, Adam, Julien, Libenciuc, Cristina, Routier, Emilie, Roy, Séverine, Désaubry, Laurent, Eggermont, Alexander M., Sonenberg, Nahum, Scoazec, Jean Yves, Eychène, Alain, Vagner, Stéphan, and Robert, Caroline
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- 2018
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8. Interplay Between Diabetes and Pancreatic Ductal Adenocarcinoma and Insulinoma: The Role of Aging, Genetic Factors, and Obesity
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Bertrand Duvillié, Rayane Kourdoughli, Sabine Druillennec, Alain Eychène, and Celio Pouponnot
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diabetes ,pancreas ,cancer ,aging ,insulinoma ,obesity ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Epidemiologic analyses have shed light on an association between type 2 diabetes (T2D) and pancreatic ductal adenocarcinoma (PDAC). Recent data also suggest a potential relationship between T2D and insulinoma. Under rare circumstances, type 1 diabetes (T1D) can also be implicated in tumorigenesis. The biological mechanisms underlying such relationships are extremely complex. Some genetic factors contributing to the development of T2D are shared with pancreatic exocrine and endocrine tumors. Obesity and overweight can also contribute to the initiation and severity of T2D, while aging may influence both endocrine and exocrine tumors. Finally, pharmacological treatments of T2D may have an impact on PDAC. On the other hand, some treatments for insulinoma can trigger diabetes. In the present minireview, we discuss the cellular and molecular mechanisms that could explain these interactions. This analysis may help to define new potential therapeutic strategies.
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- 2020
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9. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study
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Hausfater, Pierre, Pourriat, Jean-Louis, Casalino, Enrique, Riou, Bruno, Pateron, Dominique, Yéni, Patrick, Bricaire, François, Ville, Yves, Azria, Elie, Dommergues, Marc, Bergmann, Jean-François, Wolff, Michel, Mira, Jean-Paul, Guillevin, Loïc, Zuber, Mathieu, Abasse, Soumeth, Aberrane, Saïd, Abgueguen, Pierre, Abokasem, Ayman, Abraham, Bruno, Ache-Papillon, Chantal, Adam, Pascal, Adam, Marie-Noëlle, Adhoute, Xavier, Adoue, Daniel, Afi, Moncef, Afroukh, Nawel, Agha-Mir, Ilhem, Aissa, Nejla, Aissaoui, Liamine, Akerman, Grégory, Akkari, Ali, Al Chaar, Majed, Al Freijat, Faraj, Al-Jalaby, Bachar, Albert, Didier, Albertini, Marie-Thérèse, Albinet, Hélène, Alfonsi, Gwenaël, Ali, Youssef, Chaouche, Zahr-Eddine Ali, Allart, Anne, Alric, Laurent, Améri, Alain, Amoura, Zahir, Ampère, Alexandre, Amroun, Hakim, Ananivi, Amévi, Ancelin, Pascal, André, Thierry, Andremont, Antoine, Andreotti, Dominique, Andriamaneo, Hélinoro, Andriau, Clara, Anglaret, Hélène, Anguel, Nadia, Annaix, Véronique, Anteur, Wassila, Anuset, Delphine, Aoudia, Ourida, Arabi, Miloud, Archambaud, Muriel, Archambaud, Maryse, Ardiet, Emmanuel, Argaud, Laurent, Arista, Sophie, Arlet, Guillaume, Armengaud, Jean, Arnal, Jean-Michel, Arnault, Isabelle, Arsène, Olivier, Assaf, Ziad, Assi, Assi, Assouline, David, Astruc, Dominique, Aubard, Yves, Aubert, Claude, Aubry, Jean-Paul, Auburtin, Marc, Aucher, Philippe, Audeguy, Philippe, Audié, Jean-Pierre, Aumaitre, Hugues, Aumersier, Michel, Auroux, Jean, Autret, Fanny, Auvray, Etienne, Ayach, Badih, Aye, Paul, Ayouz, Khélifa, Bachelier, Marie-Nadège, Badia, Thomas Bachelot Philippe, Badila, Patrice, Bador, Julien, Badurescu, Viorica, Baldesi, Olivier, Bandaly, Françoise, Bandin, Olivia, Bani-Sadr, Firouzé, Bannier, Stéphanie, Baranger, Thierry, Barazer, Isabelle, Barbier, Marie-Christine, Barbier, François, Barbier, Carole, Barbieux, Marianne, Marie, Barboteau, Annick, Barbut, Patricia, Baret, Mylène, Barière, François, Baril, Jean-Yves, Barillot, Isabelle, Barjon, Geneviève, Barnaud, Guilène, Barraduc, Régine, Barraud, Francis, Barraud, Olivier, Barre, Eric, Barrelet, Audrey, Barrier, Jocelyn, Bart, Fréderic, Barthélémy, Gérard, Baty, Gaëlle, Baud, Olivier, Baudel, Jean-Luc, Bay, Jacques-Olivier, Bay, Jérôme, Bazin, Claude, Beague, Sébastien, Beal Ardisson, Dominique, Beaune, Bertrand, Beauplet-Lepage, Anne, Bébéar, Cécile, Bechade, Dominique, Becherrawy, Céline, Becker-Schneider, Michelle, Bednarek, Nathalie, Bedock, Bernard, Begon, Edouard, Bekguesmia, Zaineb, Belaisch-Amart, Joëlle, Belhadj, Karim, Belle, Evelyne, Belmonte, Olivier, Belot, Jean-Pierre, Bemrah, Abdelkader, Ben Soltana, Mouna, Benbara, Amélie, Benddif-Fin, Faiza, Bénézit, François, Benifla, Jean-Louis, Benjelloul, Amine, Benkaci, Yacine, Benkhelil, Abdelaziz, Benoit-Cattin, Thierry, Benoit-Coustou, Sophie, Bensadoun, René-Jean, Bensaid, Thierry, Jacques Bensaude, Raoul, Bérard, Henri, Bercot, Béatrice, Berdin, Bruno, Berger, Marc, Berger, Pierre, Bergheul, Smail, Bergues, Benoît, Berland, Yvon, Bernard, Claude, Bernard, Louis, Bernardaud, Bérangère, Bernardi, Franck, Bernardin, Gilles, Bernasconi, François, Bert-Marcaz, Patrick, Berteaux, Béatrice, Berth-Farges, Anne, Berthelot, Gilles, Berthet, Jean, Bertrand, Kevin, Bertrou, Anne, Besnard, Marianne, Bessede, Emilie, Bethery, Philippe, Beuscart, Claude, Beyne-Rauzy, Odile, Beytout, Jean, Bezian, Marie-Christine, Bicais, Brigitte, Bidart, Sabine, Bidault, Christian, Biessy, Hélène, Bigot, Pierre, Bildea, Adrianna, Bille, Emmanuelle, Billy, Christophe, Biron, Nathalie, Bizet, Jérôme, Blaise, Didier, Blaise, Agathe, Blaison, Gilles, Blaka, Mariam, Blanc, Pierre, Blanc, Stéphane, Blanc-Amrane, Véronique, Blanchard, Pierre, Blanchard-Marche, Geneviève, Blancs, Michèle, Blazejewski, Caroline, Bléher, Yves, Blewoussi, Koffi, Blondet, Romain, Blot, François, Blum, Georges-Fabrice, Bodson, Lucien, Boidin, Emilie, Boileau, Julien, Boileau, Pascal, Boin-Gay, Véronique, Boisseau, Martial, Boisselier, Christine, Bollaert, Pierre-Edouard, Bolot, Pascal, Bonacorsi, Stéphane, Bonfils, Marie, Bonitchi, Pascal, Bonnan, Mickael, Bonnefoy, Philippe, Bonnet, Delphine, Bonnet, Richard, Bonnin, Emmanuelle, Bor, Jacques, Borie, Marie-Françoise, Borstein, Bernard, Bossi, Philippe, Botreau, Yves, Bottero, Julie, Bouasria, Abderrezak, Bouaziz, Radia, Bouchaud, Olivier, Bouche, Flore, Bouchet, Gérard, Bouden, Vincent, Boudhane, Amar, Boudy, Carole-Anne, Boue, François, Bouet, Cédric, Claude Boufetteau, Jean, Bouffandeau, Bernard, Bouhour, Damien, Bouiller, Marc, Bouillet, Laurence, Bouissou, Antoine, Boulain, Luc, Bourgeois, Stéphane, Bourgerette, Evelyne, Bourlet, Anne, Bourlière, Marc, Bourrée, Thomas, Bourrouillou, Aude, Boussekey, Nicolas, Boussier, Remi, Boutoille, David, Bouyer, Jean-Luc, Bouyssou-Destriau, Denise, Bouziges, Nicole, Boyer, Michelle, Braem, Louis, Branger, Bernard, Branger, Catherine, Brasme, Lucien, Bray, Philippe, Brazille, Patricia, Bresson, Violaine, Bret, Laurent, Breton, Anne-Laure, Breuil, Jacques, Brevet, Françoise, Briaud, Michel, Bridoux, Delphine, Briend, Delphine, Briere, Anne-Isabelle, de la Hosseraye, Claire Briere, Brieu, Nathalie, Brieux, Jean-Philippe, Brihier, Hélène, Brisou, Patrick, Brival, Marie-Laure, Broche, David, Brochen, Joëlle, Bron, Camille, Bronet, Nathalie, Bronner, Jacques, Bronowicki, Jean-Pierre, Brosset, François, Brottier-Mancini, Elisabeth, Brovedani, Sophie, Bruley des Varannes, Stanislas, Brunel, Pascale, Brunet, Patrick, Brunet, Xavier, Brunet, Stéphanie, Brung-Lefebvre, Maud, Brunot, Vincent, Brusset, Alain, Burc-Struxiano, Laurence, Burdin, Michèle, Bureau, Thierry, Buron, Fanny, Burucoa, Christophe, Cabalion, Jean, Cabasson, Severine, Cabié, André, Cacheux, Victoria, Cadiergue, Vincent, Cadiot, Guillaume, Caille, Vincent, Cailleaux Pierre-Etienne Cailleux, Vincent, Caillon, Jocelyne, Caillot, Denis, Camara, Mohamed, Cambau, Emmanuelle, Cambonie, Gilles, Camiade, Sabine, Canis, Frederique, Canitrot, Meriem, Canu, Nathalie, Capellier, Gilles, Carbillon, Lionel, Carbonelle, Bernard, Carbonelle, Etienne, Carboni, Marion, Carbonne, Bruno, Carcenac, Francis, Cardot, Florence, Carette, Sylvie, Cariou, Sylvie, Carli, Pierre, Carmagnol, Françoise, Caroli-Bosc, François-Xavier, Caron, François, Cartron, Guillaume, Casali, Patrick, Casanovas, Olivier, Cassignard, Dominique, Castaing, Denis, Castel, Brisse, Castelin, Sandrine, Castelnau, Pierre, Cathebras, Pascal, Catineau, Jean, Catteu, Sylviane, Cattier, Blandine, Cattoen, Christian, Cattoir, Vincent, Caumes, Eric, Caussin, Jean, Cavalié, François, Ceppa, Franck, Cerf, Charles, Ceriez, Anne, Cervantes, Nathalie, Chabanon-Pouget, Bruno, Chabrol, Amélie, Chachaty, Elisabeth, Chahtour, Hanen, Chaix, Fabrice, Challier, Marion, Chalvon-Demersay, Arnaud, Chambreuil, Guy, Chaminade, Bruno, Chamouine, Abdourahim, Chandesris Joséphine Chapalain-Cagnon, Christine, Chapelle, Alain, Chaplain, Chantal, Chapuzet, Claire, Charachon, Sylvie, Charasse, Christophe, Charbonnier, Thierry, Charlier, Franck, Chassin, Olivier, Chassy, Véronique, Chatellier, Delphine, Chatron, Marlène, Chaussade, Hélène, Chavanet, Pascal, Chavel, Pascale, Chekroun, Ali, Chelle, Wladimir, Chelly, Jonathan, Cherlet, Christel, Chevailler, Alain, Chevalet, Pascal, Chevalier, Yannick, Chidiac, Christian, Chimot, Loïc, Chiouk, Nabil, Chiron, Philippe, Chirouze, Catherine, Chopin, Marie-Charlotte, Choukroun, Gabriel, Chouraqui, Martine, Chraibi, Kamilla, Chudersky, Dominique, Chuzeville, Michel, Cingotti, Michel, Cinquetti, Gael, Ciocan, Dragos, Citony, Isabelle, Claise, Catherine, Clarissou-Philippe, Juliette, Claude, Benoît, Clave, Danielle, Clément, Christophe, Climas, Marie-Thérèse, Coetmeur, Daniel, Cognet, Stéphanie, Cohen, Daniel, Coignard, Sophie, Coindre, Jean-Philippe, Coint, Raphaël, Colamarino, Renato, Colingorski, Anne-Marie, Collard, Olivier, Collet, Michel, Collignon, Anne, Collus, Marie-José, Colombani, Jean-Claude, Colombat, Philippe, Combe, Christian, Condominas, Philippe, Conroy, Marie-Chrsitine, Constans, Thierry, Constantin, Nicole, Contamin, Claudine, Corberand, Damien, Cordier, Anne-Marie, Cordonnier, Charlotte, Corneloup, Hélène, Costa, Yannick, Costa, Frédérique, Coste, Mathieu, Costes, Corinne, Cotes, Françoise, Cotteret, Rabea, Couderc, Louis-Jean, Cougoul, Pierre, Coulaud, Jean-Michel, Coulhon, Marie-Pierre, Coulon, Patrice, Courcol, René, Courillon, Florence, Courjon, Johan, Courouble, Jérémie, Courouge-Dorcier, Dominique, Courtade, Henri, Courtois, Stéphanie, Couturier, Pascal, Créange, Alain, Cremet, Lise, Cremniter, Julie, Croize, Jacques, Crombe, Valérie, Croquet, Ingrid, Cua, Eric, Cufi, Marie-Noelle, Cuvillier, Patrice, Dabysing, Marie-Françoise, Dadoun, Karim, Dagada, Corinne, Dahan, Sonia, Dahoumane, Redouane, Daleas, Jacques, Dallay, Dominique, Dalle, Benoît, Damage, Alexandre, Damaj, Lena, Damaj Gandhi, Laurent, Danalaché, Ana, Danin, Pierre-Eric, Danjean, Marie-Pierre, Danquechin Dorval, Etienne, Dao, Anne, Daoud, Patrick, Darchen, Olivier, Dargère, Sylvie, Darre, Bincy, Dassant, Damien, Dassieu, Gilles, Dattin-Dorrière, Valérie, Daupin, Cedric, Daurel, Claire, Dausset, Jean-Claude, Daval Cote, Mélanie, David, Gary, Davido, Benjamin, De Barbeyrac, Bertille, De Biasi, Michel, De Boysson, Hubert, De Clareuil, Edith, De Kermadec, Jean-Michel, De Martino, Sylvie, De Tayrac, Renaud, De Varax, Roland, De Witte, Sten, Debernardi, Anne, Deboutin, Jean-Luc, Debouverie, Marc, Decoene, Christophe, Decoster, Anne, Decousser, Jean-Winoc, Decré, Dominique, Defebvre, Renaud, Degand, Nicolas, Degreff, Jean-Marc, Deiber, Michel, Delaby, Hélène, Delacour, Thierry, Delahaye, Arnaud, Delarbre, Jean-Marie, Delasalle, Chantal, Delbrouck, Claire, Delecalle, Jean-Gilles, Delesalle, Sophie, Delesalle, Chantal, Delhoustal, Laurence, Deligne, Delphine, Delisle Mizon, Françoise, Delobel, Pierre, Delour, Pierre, Delpeuch, Bruno, Demachy, Marie-Claude, Demarchi, Martin, Demarcq, Marie-Joelle, Demontclos, Henri, Dengo, Jean-Christophe, Deprecq, Sophie, Dequin, Pierre-François, Dereeper, Olivier, Deroux, Alban, Derragui, Aicha, Desblache, Julien, Desbois-Nogard, Nicole, Descamps, Dominique, Descamps, Jean-Michel, Deschamps, Christophe, Deschamps, Jacques, Desemerie, Franck, Desfrere, Luc, Desliers, Joelle, Desnoulez, Laurence, Desplaces, Nicole, Després, Nicolas, Dessin, Jean-François, Destors, Marie, Detante, Olivier, Detave, Mathieu, Detourmignies, Laurence, Devaud, Edouard, Devaux, Yves, Devaux, Bruno, Devianne, François, Devidas, Alain, Devos, Philippe, Dewitte, Camille, Dewulf, Gisèle, Dhennain, Chantal, Di Meglio, Chloé, Diallo, Habiboulaye, Diamantis, Sylvain, Dib, Baihas, Didier, Jean-Marc, Dillies, Anne-Françoise, Dingremont, Claire, Djafari, Noureddine, Djeffal, Abdelmajid, Djerad, Hama, Dollon, Christophe, Doloy, Alexandra, Domart, Yves, Donay, Jean-Luc, Dopeux, Loïc, Dorr, Gaelle, Doucet Populaire, Florence, Dournon, Nathalie, Dreyfus, Michel, Dreyfuss, Didier, Du Cheyron, Damien, Dubois, Elodie, Dubois, Nicolas, Dubosc-Marchenay, Nadine, Dubourdieu, Béatrice, Dubroca, Nadine, Dubus, Jean-Christophe, Duche, Catherine, Duchene, Francis, Dudeffant, Patrick, Duez, Jean-Marie, Duhaut, Pierre, Duluc, Françoise, Dumouchel, Hélène, Dumoulard, Bruno, Dupin, Clarisse, Dupon, Michel, Dupont, Mathieu, Dupont, Damien, Dupont, Patrick, Dupre-Narlet, Emmanuelle, Dupretz, Peggy, Dupuy, Claire-Antoinette, Durand, Michel, Durand, Annie, Durliat-Ellie, Solène, Durox, Hélène, Dussopt, Christine, Dutasta, Fabien, Duval, Véronique, Dzeing, Ella, Eboue, Florence, Ede, Cyrille, Eid, Hanna, El Yamani, Abderrazak, Elbez, Annie, Eldeghedy, Mohamed, Elena-Daumas, Martine, Elhadad, Simon, Elharie-Heraux, Zoubida, Eloy, Clarence, Emeriau, Marie-Etiennette, Emond, Jean-Philippe, Equy, Véronique, Erena-Penet, Anne-Sophie, Esnault, Cecilia, Esposito, Laure, Essouri, Sandrine, Estépa, Laurence, Estève, Vincent, Etchemendy, Sabine, Ettahar, Nicolas, Eustache, Marie-Line, Evillard, Mathieu, Evreux, Françoise, Eychene, Jean-Marc, Eyer, Didier, Eymerit, Philippe, Fabre, Jean-Luc, Fabre, Claire, Faibis, Frédéric, Falchero, Lionel, Falguières, Odile, Fallouh, Hassan, Fanjaud, Nicolas, Fantin, Bruno, Farah, Ibrahim, Farto-Bensasson, Fernanda, Fauchais, Anne-Laure, Fauchart, Jean-Pierre, Faucher, Anna, Faucheux, Jean-Marc, Faudon-Gibelin, Anne, Faurie, Pierre, Fèbre, Claudine, Feddal, Toufik, Ferhat Carre, Assia, Ferreira-Maident, Nicole, Ferreyra, Milagros, Ferroni, Agnès, Ferry, Tristan, Feugier, Pierre, Feugier, Jean-Claude, Fezoui, Hacene, Fiette, Hélène, Fille, Alexandra, Filloux, Jean-Michel, Fily, Fabien, Fines, Marguerite, Fissore Magdelein, Cristel, Flahault, Mathilde, Floriot, Christian, Foguem, Clovis, Fonsale, Nathalie, Fontenel, Benoît, Forest, Anne-Marie, Forest, Anne, Forestier, Emmanuel, Fortin, Louise, Fortineau, Nicolas, Fos, Marie-Pierre, Foucart, Saskia, Fouilhoux, Alain-Charles, Fournel, Pierre, Fournier, Damien, Fourrier, François, Fraisse, Thibaut, Fredenucci, Isabelle, Fremin-Batteux, Odile, Frey, Janine, Frimat, Luc, Froidure, Marie, Fruchart, Christophe, Fruleux, Nathalie, Fuhrmann, Christine, Fuillet, Michel, Funakoshi, Nathalie, Fur, Alain, Gabez-Therou, Patricia, Gaborieau, Valerie, Gabriel-Soléan, Sylvie, Gachassin, Laurence, Gaide, Jean-François, Gaillard, Julia, Gaillard, Jean-Louis, Gaillart, Tiphaine, Gaizi, Sad, Gallo, Nicolas, Gameiro, Manuel-Luis, Garandeau, Caroline, Garbi, Aurelie, Garcera, Yves, Gardes, Ghislaine, Garesslin, Olivier, Garnier, Fabien, Garofano, Marie, Garosi, Olivier, Garre, Michel, Garrec, Hélène, Garrigues, Bernard, Gaschet, Anne, Gascon, Alexandre, Gascou, Emmanuel, Gasnault, Jacques, Gatfosse, Marc, Gattault, Jean-François, Gatti, Hélène, Gauche, Bernard, Gaudard, Philippe, Gaudelus, Joel, Gaudry, Stéphane, Gauduchon, Valérie, Gaulthier, Jean-Baptiste, Gauthier, Yvan, Gebeile, Rémi, Geffray, Loïc, Geffroy, Françoise, Geissler, Alain, Gelez, Maud, Gendrin, Vincent, Gengembre, Guy, Gentilhomme, Hervé, Gérart Pons, Sandrine, Germain, Marie-Claude, Gesquière, Julien, Ghedira, Adel, Ghevaert, Christine, Gillot, Jean-Michel, Girard, Edouard, Girard, Serge, Girard, Pierre-Marie, Girard-Buttaz, Isabelle, Giraud, Martine, Glorieux, Isabelle, Goburdhun, Chandrah, Godin, Michel, Godon, Catherine, Goehringer, François, Goffart, Sylvie, Goidin, Isabelle, Goldgran Toledano, Daniele, Golfier, François, Goll, Armand, Gontieron, Olivier, Goquelin, Anne, Got, Laurence, Goudeau, Alain, Goujard, Cécile, Goupil, François, Gouraud, François, Gourlaouen, Alain, Gournay, Jérôme, Goustille, Julien, Goux, Alain, Grandclerc, Benoît, Grange, Jean-Didier, Granger, Thierry, Granier, Françoise, Granier, Michèle, Grasset, Denis, Gravet, Alain, Grawey, Isabelle, Greder Belan, Alix, Grelaud, Jean-Jacques, Grenet, Karine, Gressier, Bernard, Grignon, Bernadette, Grimprel, Emmanuel, Grise, Geneviève, Grobost, Vincent, Gross Goupil, Marine, Grossi, Olivier, Gruffat, Brigitte, Gruson, Anne, Guénard, Yves, Guérard, Arnaud, Guérin, Bruno, Guérin, Mathilde, Guérin, Claude, Guerquin, Bernard, Guerrot, Dominique, Guéry, Benoît, Gueudet, Philippe, Gueugniaud, Pierre-Yves, Guichard, Isabelle, Guichart, François, Guiden, Ozel, Guider, Bertrand, Guillarmé Grossmann, Pascale, Guillemot, François, Guillet, Pierre, Guillet-Caruba, Christelle, Guillois, Bernard, Guilloy, Olivier, Guimard, Thomas, Guimard, Karine, Guimier, Philippe, Guinard, Jérôme, Guinet, François, Guisset, Olivier, Guitteaud, Karine, Gutmann, Laurent, Guyetand, Severine, Haccourt, Fabian, Hacot, Jean-Pierre, Hadou, Tahar, Haiat, Stéphanie, Haioun, Corinne, Hajjar, Mostapha, Hamitou, Zakaria, Hammami, Sarah, Hamon-Charles, Sophie, Hamou-Plotkine, Laurence, Hanouz, Jean-Luc, Harbi, Samia, Harlé, Jean-Robert, Haro, Sophie, Harou, Christian, Harvey, Thierry, Hatem, Ghada, Hausermann, Marie-Hélène, Hauss, Pierre-Alexandre, Hayoun, Fabrice, Hecham, Moussa, Heches, Xavier, Hedjem, Nourredine, Heidt, Anne, Heisel, Nicolas, Heluwaert, Fréderic, Helvadjian, Thierry, Henni, Tawfiq, Henry-Andrieu, Yanne, Hequet, Delphine, Herbecq, Patrick, Herbrecht, Raoul, Hernu, Romain, Herry, Catherine, Herry, Jean-Paul, Herson, Serge, Heurtaux, Marie-Noelle, Heusse, Emmanuelle, Heyraud-Blanchet, Catherine, Hichri, Yoar, Hilbert, Gilles, Hili, Marie-Thérèse, Hiret, Sandrine, Hittinger, Gilles, Hochart, Anne-Cécile, Hodee, Nathalie, Holstein, Anne, Hombrouk-Alet, Cécile, Hominal, Stéphane, Honderlick, Patrick, Honoré Bouakline, Stéphanie, Hory, Bernard, Hourdebaigt-Larrusse, Pierre, Houssaye, Serge, Houssiaux-Maisonneuve, Nathalie, Hrichi, Abdelkader, Hubert, Didier, Huc, Benoît, Humbert, Karine, Hurel, Dominique, Husson-Wetzel, Stéphanie, Hutin, Pascal, Huttin, Bernard, Hyerle, Laura, Iacobelli, Silvia, Ilunga, Serge, Imbert, Guenièvre, Jabre-Sikias, Elias, Jacob, Jean-Louis, Jacobs, Romain, Jacomy, Dominique, Jacquier, Pascal, Jacquier, Hervé, Jaffarbandjee, Marie-Christine, Jamet, Angéline, Jan, Didier, Jang, Guyro, Jaouen, Anne-Christine, Jardel, Henry, Jarlier, Vincent, Jarrige, Luc, Jarrousse, Bernard, Jauhlac, Benoît, Jault, Véronique, Jault, Thierry, Jaunait, Eric, Javouhey, Etienne, Jean, Rodolphe, Jean, Julie, Jean-Pierre, Hélène, Jeanmaire, Eliette, Jeannot, Katy, Jeddi, Hassen, Jego, Mickael, Jennane, Selim, Join-Lambert, Olivier, Joly, Pascal, Jonquet, Olivier, Josien, Eric, Jouatte, Fabienne, Jouffret, Agnès, Jourde-Chiche, Noémie, Jourdes, Emilie, Jouvencel, Philippe, Jouzel, Charlotte, Julienne, Geneviève, Jullian, Eric, Juven, Agnès, Juvin, Philippe, Kaidomar, Michel, Kaiser, Thomas, Kalfon, Pierre, Kaltenbach, Georges, Kamar, Nassim, Kansau, Imad, Kara, Ali, Karaoui, Leila, Karirisi, Apollinaire, Karkous, Bernard, Kassis, Marie, Kayal, Samer, Keller, Marie, Kemenar, Chrystelle, Kennouche, Samir, Kerchache, Aissa, Kerleau, Jean-Marc, Kervegant, Anne-Gaelle, Khalifa-Thellier, Sandrine, Radhouane-Khanjari, Fethi, Kherouf, Hakim, Khodeir, Nordine, Kibbrecht, Eric, Kim, An, Kisterman, Jean-Paul, Kittschke, Bernard, Klapczynski, Frédéric, Kodzin, Marie-José, Konate, Bano, Kouaho, Sylvain, Koulmann, Laurence, Krechiem, Karim, Kubab, Sarah, Kubiak, Charles, Kurtz, Jean-Emmanuel, Labadie, Philippe, Labarrière, Damien, Labaune-Kiss, Andrea, Labé, Aurélie, Labourdette, Isabelle, Labrousse, Philippe, Labussière, Anne-Sophie, Lachenal, Florence, Lacroix, Jérôme, Lafeuillade, Alain, Lafforgue, Marie-Odile, Lafon, Ingrid, Lagasse, Jean-Pierre, Lagrandeur, Julien, Lalot, Jean-Marc, Lalu, Mélissa, Laluque, Simone, Lamache, Sébastien, Lamarca, Richard, Lamberet, Aurore, Lambert, Thierry, Lambiotte, Fabien, Lamia, Bouchra, Lamoine-Gimet, Ghislaine, Lamour, Armelle, Lamy, Brigitte, Lanba, Patrice, Landgraf, Nathalie, Landraud, Luc, Laporte, Jean-Patrick, Larible, Claire, Larrazet, Fabrice, Larroche, Claire, Lasbasses, Claudine, Lassel, Ludovic, Lassere, Bertrand, Laudat, Patrice, Lauque, Dominique, Laurens, Etienne, Laurent, Frédéric, Lauretta, Raphael, Laurin, Max, Lauzanne, Brigitte, Lavalard, Emmanuelle, Lavenu, Isabelle, Lavigne, Jean-Philippe, Le Baron, François, Le Berre, Rozenn, Le Berruyer, Pierre-Yves, Le Bideau, Marc, Le Boterff, Cécile, Le Chevallier, Sylvain, Le Coustumier, Alain, Le Du, Anne, Le Goff, Valérie, Le Henaff, Catherine, Le Lay, Geneviève, Le Maout, Gilles, Le Pierres, Athéna, Le Pimpec, Patricia, Le Poulain, Marguerite, Le Reste, Anne-Marie, Le Sec, Ludovic, Le Turdu, Françoise, Leautez-Nainville, Sophie, Lebas, Eddy, Leblond, Véronique, Lebreton, Marie-Annick, Lebreton, Didier, Lecaillon-Thibon, Evelyne, Lechat, Sylvie, Lechiche, Catherine, Lecis, Alain, Leclercq, Roland, Lecomte, Claire, Lécuyer, Hervé, Ledru, Sylvie, Leduc, Dominique, Leflon, Véronique, Lefort, Christine, Lefranc, Hélène, Lefrant, Jean-Yves, Legendre, Christophe, Legoff, Isabelle, Legout, Laurence, Legrand, Mathieu, Legras, Annick, Legros, Antoine, Leguen, Virginie, Leibinger, Franck, Lelièvre, Jean-Daniel, Lellouche, Franck, Lemaignen, Adrien, Lemarie, Romain, Lemble, Chantal, Lemenand, Olivier, Lemercier, Fanny, Lemery, Didier, Lemmens, Bruno, Lemyze, Malcolm, Leneveu, Michel, Léonetti, Françoise, Léonnet, Caroline, Léotard, Sophie, Lepeletier, Didier, Lepelletier, Didier, Lepeule, Raphael, Lepiller, Quentin, Lequen, Laurence, Leroux, Lionel, Leroux, Stéphane, Leroy, Hélène, Leroy, Vincent, Leroy, Olivier, Lesage, Fabrice, Lescat, Mathilde, Lesecq, Ludovic, Lessene, Aude, Lessinger, Jean-Marc, Letellier, Claire, Letellier, Nicolas, Letouzey, Vincent, Letranchant, Lorraine, Levast, Marion, Leveneur, Yann, Levent, Thierry, Levy, Marie, Levy, Marc, Leysenne, David, Libeau, Benoît, Likose, Ebutu, Lima, Suzanne, Lina, Gérard, Lioger, Bertrand, Lionnet, Benoît, Lipovac, Anne-Sophie, Loffeier, Vincent, Loison, Françoise, Lorchleac'h, Aurélien, Lorge, Fabienne, Loriferne, Jean-François, Lorléa'ch, Aurélien, Louart, Guillaume, Loury-Lariviere, Isabelle, Loustaud, Véronique, Lozniewski, Alain, Luciani, Roger-Charles, Luminitan Elena Lupean, Luca, Lureau, Pierre, Lutz-Murphy, Marie-France, Mbimba, Luwawu, M'Bey, Damien, Maakaroun, Abdallah, Macci, Valérie, Magdoud, Fatma, Mager, Guy, Magna, Théophile, Magny, Jean-François, Mahaza, Chetaou, Mahé, Isabelle, Maillard, Christine, Maillet, Jean-Jacques, Maillet, François, Maillez, Sébastien, Maillot, François, Maisonneuve, Antoine, Makdessi, Solène, Malbrunot, Claire, Malbruny, Brigitte, Malderet, Caroline, Malfuson, Jean-Valère, Malherbe, Philippe, Malherbe, Patrick, Malhiere, Sophie, Mandelbrot, Laurent, Mandin, Laurent, Mandjee, Aziza, Manéglier, Benjamin, Mansouria, Mohammed, Marcu, Elena, Mariette, Jean-Bernard, Mariette, Sylvie, Markarian, Jacques, Marmouset, Carole, Marpeau, Olivier, Marret, Olivier, Marsepoil, Thierry, Marterl-Lafay, Isabelle, Martha, Benoît, Marthelet, Patrick, Martin, Xavier, Martin, Florence, Martin, Pierre, Martin, Régine, Martin, Christian, Martin Lefèvre, Laurent, Martineau, Olivier, Martinet, Olivier, Martinez, Valérie, Martinot, Martin, Martres, Pascale, Marty, Sophie, Marty-Ane, Charles, Marzouk, Paul, Mascade, Géraldine, Masia, Florent, Masseron, Thierry, Masson, Loïc, Masson, Philippe, Matheron, Isabelle, Matica, Slavius, Matray, Olivier, Mattei, Marie-Françoise, Maubert, Bertrand, Maugein, Jeanne, Maureira, Juan-Pablo, May, Thierry, May, Adrien, Maze, Vincent, Meaudre Desgouttes, Eric, Mebazaa, Alexandre, Mechai, Frédéric, Medeau, Virginie, Megbemado, Richard, Mehri, Mona, Mein-Bottini, Myriam, Melis, Adrien, Mellier, Joelle, Ménager, Philippe, Ménard, Céline, Mendes-Martin, Lucile, Menguy, Anne-Claude, Menouar, Mohamed, Merabet, Taoufik, Mercury, Paul, Meregnani, Corinne, Mérigot, Philippe, Mermont, Sylvain, Merrouche, Yacine, Merville, Pierre-Gilles, Mesnage, Renaud, Mesnard, Louis, Messager, Aurélie, Messiaen, Thierry, Messika, Jonathan, Messner Pellenc, Patrick, Métenier, Hervé, Metton, Pierre, Meyer, Christian, Mialon, Michel, Miatello, Jordi, Michaud-herbst, Alban, Michault, Alain, Micheli, Sophie, Michon, Jocelyn, Baptiste Michot, Jean, Mielczarek, Severine, Mignart, Sophie, Mignaut, Virginie, Migraine Bouvagnet, Audrey, Mihout, Fabrice, Mille, Catherine, Millet, Olivier, Milpied, Noel, Mimoz, Olivier, Minet, Jacques, Minguet, Bertrand, Mohty, Mohamad, Moiton, Marie-Pierre, Monarchi, Richard, Monceau, Yannick, Monchi, Mehran, Monlun, Eric, Monsegu, Jacques, Montagne, Nathalie, Montcriol, Ambroise, Montmasson, Bernard, Mootien, Paramasiven, Moquet, Olivier, Morando, Virginie, Moreau, Anne-Sohie, Morel, Yves, Morelon, Emmanuel, Morin-Fatome, Armelle, Morincomme, Mathieu, Morlat, Philippe, Mosser, Laurent, Motard-Picheloup, Annie, Mottaz, Philippe, Moulinoux, Claire, Mouly, Laurence, Mourad, Georges, Mouries, Jean-Claude, Moussa, Hecham, Moustache, Audrey, Muir, Jean-François, Murbach, Valérie, N'guyen, Yohann, N'guyen, Jean-Claude, N'guyen-Khac, Florence, Nabholtz, Jean-Marc, Naceur, Tarik, Nakhleh, Jean, Nare, Aline, Nassif, Xavier, Nathan-Bonnet, Frédérique, Negrery, Huguette, Negrier, Claude, Neri, Dominique, Nesrine, Hakima, Neuwirth, Catherine, Ngami, Eugène, Carole Ngo Bell, Elisabeth, Nicobaharaye, Dieudonné, Nicolet, Laurent, Nicolet, Laurence, Nicolino, Marc, Niel, Philippe, Nikodijevic, Karine, Nkunzimana, Jean-Marie, Noel, Christian, Noirot, Alain, Noto, Philippe, Noulard, Marie-Noelle, Ntalu Nkato, Christophe, Nyunga, Martine, Obiols, Julien, Ochocki, Patrick, Odent, Sylvie, Olivier, Brigitte, Oliviero, Gérard, Ondze, Basile, Orléva, Oléna, Orode, Paul, Osman, Henri, Oswald, Eric, Otean, Paola, Ouazir, Abderkader, Ozanon, Christophe, Paccalin, Marc, Pages, Marie-Christine, Paindaveine, Bénédicte, Pangon, Béatrice, Pannecouck, Jean-Marie, Paquet, Jean-Christophe, Parent, Sabrina, Parisi-Duchene, Elisabeth, Pasche, Jérôme, Pasdeloup, Thierry, Patin, David, Patrigeon, René-Gilles, Patry, Isabelle, Paul, Jean-Gabriel, Pavel, Simona, Pavic, Michel, Pawlotsky, Jean-Michel, Payan, Christopher, Payen, Christiane, Péan, Yves, Péchinot, Frédérique, Péchinot, André, Pecquet, Matthieu, Pélaquier, Agnès, Peltier, Hervé, Penn, Pascale, Pennaforte, Jean-Loup, Perez, Didier, Périsson, Caroline, Perotin, Dominique, Perouse de Montclos, Michèle, Perreve, Sophie, Perronne, Christian, Perrotin, Dominique, Pesque, Valerie, Pestel-Caron, Martine, Pestre, Vincent, Petassou, Fabrice, Petit, Marie-Cécile, Petit Hoang, Camille, Petitjean, Philippe, Pettinelli, François, Peultier, Anne-Sophie, Piala, Jean-Marie, Pialoux, Gilles, Piau, Caroline, Picard, Aurélia, Picaud, Jean-Charles, Pichard, Eric, Pierre, Martin, Pierre, Fabrice, Pierrot, Paul, Piet, Emilie, Piffaut, Marie-Claude, Pigeon, Bertrand, Pignon, Carole, Pinon, Georges, Piquet, Jacques, Piriou, Vincent, Placidi, Eric, Plainfosse, Gillles, Plane, Christophe, Plantier, Isabelle, Claudiu-Plesa, Nicolai, Plésiat, Patrick, Plessis, Patrick, Plouzeau-Jayle, Chloé, Ploy, Marie-Cécile, Pochmalicki, Gilbert, Pofelski, Joanna, Poinsignon, Yves, Poirier, Anne-Sophie, Poitevin, Françoise, Pommier, Christian, Ponceau, Bénédicte, Poncelet, Christophe, Pop, Daniela, Porcheron, Martine, Pordes, Réginald, Porthault, Eric, Portneuf, Marc, Pottier, Anne, Pouedras, Pascal, Poulain, Jocelyne, Poulain, Gérard, Poupet, Hélène, Pouyanne, Julien, Pouzoullic, Marie, Poyart, Claire, Pozzetto, Bruno, Prazuck, Thierry, Pressac, Dominique, Prévost, Fabrice, Prince, Sylvie, Priollet, Pascal, Proost, Olivier, Protar, Daniel, Pujade Lauraine, Eric, Pujol, Antoine, Puybasset, Louis, Puyhardy, Jean, Quentin, Vincent, Quinsat, Denis, Rabier, Valérie, Radaoui, Fouzia, Radenac, Florian, Radenne, Sylvie, Raffenot, Didier, Raffi, François, Rahmani, Hassène, Ramanantsoa, Céline, Ranchon, Guillaume, Ranta, Dana, Raoult, Didier, Rasigade, Jean-Philippe, Rassiat, Emmanuel, Raulin, Olivia, Ravaud, Alain, Ravet, Nathalie, Razafimahefa, Hasinrina, Razafimahery, Mirana, Re, Daniel, Real, Philippe, Rebattu, Paul, Rebeyrotte, Catherine, Reboul, Pascal, Reboux, Anne-Hélène, Recule, Christine, Redonnet, Jean-Philippe, Redor, Alexis, Regouby, Yves, Rémy, Claude, Renard, Gisèle, Renard, Benoît, Renou, Frédéric, Repellin, Philippe, Reveil, Jean-Claude, Revel, Valérie, Reverseau, Anne, Revest, Mathieu, Rey, Philippe, Rey, Hyacine, Rey Zermati, Jany, Reyes Ortega, Guillermo, Reynaud, Alain, Reynes, Jacques, Rezgui, Nasseur, Riahi, Jacques, Ribes, David, Ribier, Arnaud, Richard, Christian, Richardin, Florence, Riche, Agnès, Richette, Pascal, Ridah, Khalid, Riegel, Philippe, Riehl, Frédéric, Rigaux, Françoise, Rioux, Christophe, Rival, Gilles, Rivière, Brigitte, Robert, Henri, Robert, René, Robillard, Pierre-Yves, Roblin, Mélanie, Roblot, Pascal, Roblot, France, Rogeaux, Olivier, Roger, Pierre-Marie, Rohmer-Heitz, Dominique, Rolland, Christophe, Roncato-Saberane, Mariam, Ronda, Isabelle, Rondepierre, Philippe, Roque-Afonso, Anne-Marie, Rosay, David, Rose, Christian, Roseau, Jean-Baptiste, Rosello, Sophie, Rosselli, Sylvène, Rossignol, Serge, Rostaing, Lionel, Roth, Christian, Rothe, Marie-Rose, Roubert, Xavier, Rouget, Sébastien, Rouidi, Ahmed, Roulier, Philippe, Rouquet, Yannick, Rouquette-Vincent, Isabelle, Roure Sobas, Chantal, Rousseau, Sylvaine, Rousseau, Florence, Roussel, Etienne, Roussel, Jean-Christian, Roussel, Christophe, Roussellier, Patricia, Roy, Christophe, Royer, Daniel, Roze, Jean-Christophe, Rozec, Bertrand, Ruimy, Raymond, Ruppé, Etienne, Ruyer, Olivier, Sabbat, Sébastien, Saghi, Tahar, Saigne, Christophe, Sakek, Necera, Salama, Gilles, Salanoubat, Celia, Salaun-Beretta, Guenaelle, Saliba, Elie, Salles, Gilles, Salmon, Odile, Louis Salomon, Jean, Salord, Jean-Michel, Salvucci, Marina, Samson, Thierry, Sanchez, Richard, Sansot, Dominique, Saplacan, Mihaela, Saroufim, Carlo, Sauder, Philippe, Sautereau, Denis, Savare, Ferdinand, Savatier, Rim, Scemla, Anne, Schendel, Adeline, Schmitt, Anna, Schmitt, François, Schmitt, Alain, Schneerson, Morgane, Schneider, Francis, Schved, Jean-François, Schwebel, Carole, Sebban, Anthony, Secher, Aline, Sédillot, Nicholas, Sedjelmaci, Yacine, Segonds, Christine, Seignovert, Camille, Seknazi, Corinne, Semenescu, Marius, Sément, Arnaud, Semet, Jean-Claude, Semet, Guy, Sennevile, Eric, Serier, Miloud, Serre, Arnaud, Seta, Nathalie, Seyrig, Jacques-Arnaud, Sgro, Eric, Sibony-Prat, Joyce, Sicsic, Jean-Luc, Sifaoui, Farid, Signouret, Thomas, Sigur, Nicolas, Silhadi, Souad, Siméoni, Umberto, Simian, Bernard, Similowski, Thomas, Simon, Georges, Simon, François, Simonin, Catherine, Sirbu, Cristina, Sire, Jean-Marie, Sivadon-Tardy, Valérie, Sivery, Bruno, Slama, Michel, Smati, Salim, Sobesky, Rodolphe, Sokeng-Affoule, Hélène, Sollet, Jean-Pierre, Sommabère, André, Sondag, Daniel, Soraudeau, Florence, Sotto, Albert, Soulie, Bruno, Souply, Laurent, Souquet, Jean-Christophe, Soury, Pierre, Souweine, Bertrand, Stahl, Jean-Paul, Steibach, Marie-Isabelle, Stephan, Robin, Stoclin, Annabelle, Stolidi, Philippe, Strock, Paul, Suatean, Diana, Subra, Jean-François, Sucin, Yves, Suel, Philippe, Sullice, Marc, Szwebel, Tali-Anne, Tacchini, Laurent, Talabani-Boizot, Hana, Talarmin, Jean-Philippe, Taleb, Fethi, Tamalet, Catherine, Tamion, Fabienne, Tandonnet, Olivier, Tankovic, Jacques, Tardy, Véronique, Tassot, Christelle, Taurin, Gregory, Taylor, Sabine, Tchenio, Xavier, Tebib, Jacques, Teillet, Laurent, Teixeira, Antonio, Terki, Mustapha, Tesseydre, Sonia, Texier, Jean-Claude, Texier, Anthony, Thellier, Jean-Paul, Thibaud, Didier, Thibault, Michel, Thibaut, Freddy, Thierry, Jacques, Thoinet, Sylvie, Thomas, Pierre, Thomas, René, Thomas, Yves, Thomas, Caroline, Thore, Jean, Thouret, Jean-Marc, Thouvenin, Maxime, Thuet, Francis, Tigaizin, Ahmed, Tigaud, Sylvestre, Tiry, Catherine, Tissieres, Pierre, Tissot, Alain, Tixier, Anne, Touati, Kamel, Toubia, Marie-Lina, Toullalan, Olivier, Tourani, Jean-Marc, Tourrand, Bernadette, Touze, Yvan, Trabelsi-Jnifen, Asma, Traissac, Laurent, Anh Tran, Tu, Tran, Vanessa, Tricoire, Joelle, Tronchon, Laurent, Trouiller, Sébastien, Trystram, David, Ahmed, Becaid, Tsouria, Tuca, Mirela, Turpin, Mathilde, Vache, Bernard, Vachée, Anne, Vaillant, Christine, Valadier, Patrick, Valayer, Patrick, Valette, Xavier, Vallet, Françis, Van de Velde, Florence, Vanden Einjden, Serge, Vandenesch, François, Vande-perre, Philippe, Varin, Marie-Christine, Vary, Gwenaelle, Vaschalde, Yvan, Vassallo, Matteo, Vasse, Marc, Vasseur, Manica, Vatan, Rémi, Vaucel, Jacques, Vergnaud, Michel, Verhaeghe, Annick, Vermesch-Langlin, Annie, Vernet, Guy, Vernet Garnier, Véronique, Verrier, Virginie, Vessieres, Annie, Vialette, Véronique, Viard, Jean-Paul, Vieillard Baron, Antoine, Vighetto, Alain, Villemain, Marc, Villers, Daniel, Vilque, Jean-Pierre, Vinay, Agnès, Vincent, Didier, Vincent, Pascal, Vincent, Colette, Vincent, Simon, Vinci, Clara, Viole, Didier, Violette, Jérémie, Viquesnel, Gerard, Virlouvet, Anne-Laure, Visentin, Séverine, Vittecoq, Daniel, Vodovar, Dominique, Vrigneaud, Laurence, Vu-Thien, Hoang, Vuotto, Fanny, Wafo, Estelle, Wagner, Michel, Walid, Nicola, Walter, Elisabeth, Watson, Sarah, Weinbreck, Pierre, Weinbronn, Eva, Weiss, Emmanuel, Weitten, Thierry, Welker, Yves, Westeel, Pierre-François, Wink, Olivier, Wintenberger, Claire, Woerther, Paul-Louis, Worcel, Isabelle, Wuillai, Anne, Wurmser, Marc, Xavier, Jacob, Yazdanpanah, Yazdan, Yehia, Aihem, Yvenou, Sterenn, Zagdoun, Elie, Zagozda, Dominique, Zame, Thierry-Pascal, Zamfiri, Oana, Zanaldi, Hélène, Zandecki, Marc, Zaoui, Eric, Zarrouk, Virginie, Zarski, Jean-Pierre, Zavadil, Patrick, Zeller, Valérie, Zerbib, Franck, Zerr, Vincent, Zgarni, Lémia, Zoulim, Fabien, Zoveda, Patrick, Zuber, Pierre, Zumbo, Christian, Charlier, Caroline, Perrodeau, Élodie, Leclercq, Alexandre, Cazenave, Benoît, Pilmis, Benoît, Henry, Benoît, Lopes, Amanda, Maury, Mylène M, Moura, Alexandra, Goffinet, François, Dieye, Hélène Bracq, Thouvenot, Pierre, Ungeheuer, Marie-Noëlle, Tourdjman, Mathieu, Goulet, Véronique, de Valk, Henriette, Lortholary, Olivier, Ravaud, Philippe, and Lecuit, Marc
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- 2017
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10. RAF proteins exert both specific and compensatory functions during tumour progression of NRAS-driven melanoma
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Coralie Dorard, Charlène Estrada, Céline Barbotin, Magalie Larcher, Alexandra Garancher, Jessy Leloup, Friedrich Beermann, Manuela Baccarini, Celio Pouponnot, Lionel Larue, Alain Eychène, and Sabine Druillennec
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Science - Abstract
The melanoma-driver mutations in NRAS and BRAF are mutually exclusive but the contribution of RAF signalling downstream of NRAS remains to be clarified. Here, using mouse models, the authors show specific roles of each member of the RAF family at different stages of melanomagenesis.
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- 2017
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11. Supplementary Figure Legends 1-2 from Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1
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Arnault, Jean Philippe, primary, Mateus, Christine, primary, Escudier, Bernard, primary, Tomasic, Gorana, primary, Wechsler, Janine, primary, Hollville, Emilie, primary, Soria, Jean-Charles, primary, Malka, David, primary, Sarasin, Alain, primary, Larcher, Magalie, primary, André, Jocelyne, primary, Kamsu-Kom, Nyam, primary, Boussemart, Lise, primary, Lacroix, Ludovic, primary, Spatz, Alain, primary, Eggermont, Alexander M., primary, Druillennec, Sabine, primary, Vagner, Stephan, primary, Eychène, Alain, primary, Dumaz, Nicolas, primary, and Robert, Caroline, primary
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- 2023
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12. Supplementary Figure 1 from Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1
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Arnault, Jean Philippe, primary, Mateus, Christine, primary, Escudier, Bernard, primary, Tomasic, Gorana, primary, Wechsler, Janine, primary, Hollville, Emilie, primary, Soria, Jean-Charles, primary, Malka, David, primary, Sarasin, Alain, primary, Larcher, Magalie, primary, André, Jocelyne, primary, Kamsu-Kom, Nyam, primary, Boussemart, Lise, primary, Lacroix, Ludovic, primary, Spatz, Alain, primary, Eggermont, Alexander M., primary, Druillennec, Sabine, primary, Vagner, Stephan, primary, Eychène, Alain, primary, Dumaz, Nicolas, primary, and Robert, Caroline, primary
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- 2023
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13. Supplementary Figure 2 from Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1
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Arnault, Jean Philippe, primary, Mateus, Christine, primary, Escudier, Bernard, primary, Tomasic, Gorana, primary, Wechsler, Janine, primary, Hollville, Emilie, primary, Soria, Jean-Charles, primary, Malka, David, primary, Sarasin, Alain, primary, Larcher, Magalie, primary, André, Jocelyne, primary, Kamsu-Kom, Nyam, primary, Boussemart, Lise, primary, Lacroix, Ludovic, primary, Spatz, Alain, primary, Eggermont, Alexander M., primary, Druillennec, Sabine, primary, Vagner, Stephan, primary, Eychène, Alain, primary, Dumaz, Nicolas, primary, and Robert, Caroline, primary
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- 2023
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14. An autocrine ActivinB mechanism drives TGFβ/Activin signaling in Group 3 medulloblastoma
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Morgane Morabito, Magalie Larcher, Florence MG Cavalli, Chloé Foray, Antoine Forget, Liliana Mirabal‐Ortega, Mamy Andrianteranagna, Sabine Druillennec, Alexandra Garancher, Julien Masliah‐Planchon, Sophie Leboucher, Abel Debalkew, Alessandro Raso, Olivier Delattre, Stéphanie Puget, François Doz, Michael D Taylor, Olivier Ayrault, Franck Bourdeaut, Alain Eychène, and Celio Pouponnot
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activin ,medulloblastoma ,Smad2 ,Smad3 ,TGFbeta ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Abstract Medulloblastoma (MB) is a pediatric tumor of the cerebellum divided into four groups. Group 3 is of bad prognosis and remains poorly characterized. While the current treatment involving surgery, radiotherapy, and chemotherapy often fails, no alternative therapy is yet available. Few recurrent genomic alterations that can be therapeutically targeted have been identified. Amplifications of receptors of the TGFβ/Activin pathway occur at very low frequency in Group 3 MB. However, neither their functional relevance nor activation of the downstream signaling pathway has been studied. We showed that this pathway is activated in Group 3 MB with some samples showing a very strong activation. Beside genetic alterations, we demonstrated that an ActivinB autocrine stimulation is responsible for pathway activation in a subset of Group 3 MB characterized by high PMEPA1 levels. Importantly, Galunisertib, a kinase inhibitor of the cognate receptors currently tested in clinical trials for Glioblastoma patients, showed efficacy on orthotopically grafted MB‐PDX. Our data demonstrate that the TGFβ/Activin pathway is active in a subset of Group 3 MB and can be therapeutically targeted.
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- 2019
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15. Supplementary Figure 1 from Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1
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Caroline Robert, Nicolas Dumaz, Alain Eychène, Stephan Vagner, Sabine Druillennec, Alexander M. Eggermont, Alain Spatz, Ludovic Lacroix, Lise Boussemart, Nyam Kamsu-Kom, Jocelyne André, Magalie Larcher, Alain Sarasin, David Malka, Jean-Charles Soria, Emilie Hollville, Janine Wechsler, Gorana Tomasic, Bernard Escudier, Christine Mateus, and Jean Philippe Arnault
- Abstract
PDF file - 208K
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- 2023
16. Data from Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1
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Caroline Robert, Nicolas Dumaz, Alain Eychène, Stephan Vagner, Sabine Druillennec, Alexander M. Eggermont, Alain Spatz, Ludovic Lacroix, Lise Boussemart, Nyam Kamsu-Kom, Jocelyne André, Magalie Larcher, Alain Sarasin, David Malka, Jean-Charles Soria, Emilie Hollville, Janine Wechsler, Gorana Tomasic, Bernard Escudier, Christine Mateus, and Jean Philippe Arnault
- Abstract
Purpose: The emergence of skin tumors in patients treated with sorafenib or with more recent BRAF inhibitors is an intriguing and potentially serious event. We carried out a clinical, pathologic, and molecular study of skin lesions occurring in patients receiving sorafenib.Experimental Design: Thirty-one skin lesions from patients receiving sorafenib were characterized clinically and pathologically. DNA extracted from the lesions was screened for mutation hot spots of HRAS, NRAS, KiRAS, TP53, EGFR, BRAF, AKT1, PI3KCA, TGFBR1, and PTEN. Biological effect of sorafenib was studied in vivo in normal skin specimen and in vitro on cultured keratinocytes.Results: We observed a continuous spectrum of lesions: from benign to more inflammatory and proliferative lesions, all seemingly initiated in the hair follicles. Eight oncogenic HRAS, TGFBR1, and TP53 mutations were found in 2 benign lesions, 3 keratoacanthomas (KA) and 3 KA-like squamous cell carcinoma (SCC). Six of them correspond to the typical UV signature. Treatment with sorafenib led to an increased keratinocyte proliferation and a tendency toward increased mitogen-activated protein kinase (MAPK) pathway activation in normal skin.Sorafenib induced BRAF–CRAF dimerization in cultured keratinocytes and activated CRAF with a dose-dependent effect on MAP-kinase pathway activation and on keratinocyte proliferation.Conclusion: Sorafenib induces keratinocyte proliferation in vivo and a time- and dose-dependent activation of the MAP kinase pathway in vitro. It is associated with a spectrum of lesions ranging from benign follicular cystic lesions to KA-like SCC. Additional and potentially preexisting somatic genetic events, like UV-induced mutations, might influence the evolution of benign lesions to more proliferative and malignant tumors. Clin Cancer Res; 18(1); 263–72. ©2011 AACR.
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- 2023
17. Supplementary Figure Legends 1-2 from Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1
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Caroline Robert, Nicolas Dumaz, Alain Eychène, Stephan Vagner, Sabine Druillennec, Alexander M. Eggermont, Alain Spatz, Ludovic Lacroix, Lise Boussemart, Nyam Kamsu-Kom, Jocelyne André, Magalie Larcher, Alain Sarasin, David Malka, Jean-Charles Soria, Emilie Hollville, Janine Wechsler, Gorana Tomasic, Bernard Escudier, Christine Mateus, and Jean Philippe Arnault
- Abstract
PDF file - 72K
- Published
- 2023
18. NRAS-driven melanoma: A RAF can hide another
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Sabine Druillennec, Celio Pouponnot, and Alain Eychène
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araf ,braf ,craf ,ras ,human ,melanoma ,mouse ,resistance ,tumor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Using mouse genetics, we recently showed that BRAF has a critical role in initiation of NRAS-driven melanoma that cannot be compensated by CRAF. In contrast, RAF proteins display compensatory functions in fully established tumors and ARAF can sustain proliferation in the absence of BRAF and CRAF, highlighting an addiction to RAF signaling in NRAS-driven melanoma.
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- 2017
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19. Particularités de la dengue chez le sujet âgé
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Sautereau, N., primary, Randriamalala, F., additional, Eychène, J., additional, Maillard, O., additional, and Bertolotti, A., additional
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- 2022
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20. Effects of competitive research training funding on the careers of medical doctors
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Castagner, François, Chollet, Emmanuelle, Chomienne, Christine, de Launoit, Yvan, Eychène, Alain, and Altabef, Muriel
- Abstract
Only few laureates of a M2 degree were continuing with research activities. Although several factors are influencing the decision to engage significantly in research, as analysed by Amgad and colleagues (2015), some laureates might have done a M2 degree in research to fulfil the requirements of such a degree to pretend to senior tenure positions in a hospital department in France. A return to clinical activities between a Master 2 degree and a PhD in research was often observed, deemed by former laureates as important for clinical expertise and insured senior tenure positions. Even if the hindsight did not allow us to have the complete career paths, we observed a clear tendency for doctorate laureates to engage more in career paths involving research. The career wishes as expressed by laureates were also presenting a clear shift after a PhD with more laureates reporting wishes to have research activities, albeit mostly together with clinical work. Interestingly, the fulfilment of those wishes was also increasing with the doctorate laureates having a career mostly in accordance to the expressed wishes. The medical students of the contrafactual group were less likely to be involved in research later in their careers even though all of them did a PhD thesis funded by other means. This could be explained either by an attractiveness of the programme that successfully recruited or selected medical students interested in research or by features of the programme that allowed the laureates to perform well in research. This study on medical students laureates of research trainings therefore indicates that engaging in a PhD thesis in research is more indicative of future research activities than a Master 2 degree. The scope of the programme has been reassessed upon this analysis to focus on PhD thesis grants.
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- 2022
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21. B-Raf and C-Raf Are Required for Melanocyte Stem Cell Self-Maintenance
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Agathe Valluet, Sabine Druillennec, Céline Barbotin, Coralie Dorard, Anne H. Monsoro-Burq, Magalie Larcher, Celio Pouponnot, Manuela Baccarini, Lionel Larue, and Alain Eychène
- Subjects
Biology (General) ,QH301-705.5 - Abstract
B-Raf and C-Raf kinases have emerged as critical players in melanoma. However, little is known about their role during development and homeostasis of the melanocyte lineage. Here, we report that knockout of B-raf and C-raf genes in this lineage results in normal pigmentation at birth with no defect in migration, proliferation, or differentiation of melanoblasts in mouse hair follicles. In contrast, the double raf knockout mice displayed hair graying resulting from a defect in cell-cycle entry of melanocyte stem cells (MSCs) and their subsequent depletion in the hair follicle bulge. Therefore, Raf signaling is dispensable for early melanocyte lineage development, but necessary for MSC maintenance.
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- 2012
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22. New level of regulation of MITF activity by direct interaction with RAF proteins
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Cedric Messaoudi, Laetitia Besse, Liliana Mirabal-Ortega, Corine Bertolotto, Charlène Estrada, Celio Pouponnot, Florent Dingli, Damarys Loew, Sabine Druillennec, and Alain Eychène
- Subjects
body regions ,integumentary system ,Computational biology ,Biology ,Microphthalmia-associated transcription factor - Abstract
The MITF transcription factor and the RAS/RAF/MEK/ERK pathway are two interconnected main players in melanoma. Understanding how MITF activity is regulated represents a key question since its dynamic modulation is involved in the phenotypic plasticity of melanoma cells and their resistance to therapy. By investigating the role of ARAF in NRAS-driven melanoma through mass spectrometry experiments followed by a functional siRNA-based screen, we unexpectedly identified MITF as a direct ARAF partner. Interestingly, this interaction is conserved among the RAF protein kinase family since the formation of BRAF/MITF and CRAF/MITF complexes was also observed in the cytosol of NRAS-mutated melanoma cells. The interaction occurs through the kinase domain of RAF proteins and is correlated with their kinase activity level. RAF/MITF complexes modulate MITF nuclear localization by inducing an accumulation of MITF in the cytoplasm, thus negatively controlling its transcriptional activity. Taken together, our study highlights a new level of regulation between two major mediators of melanoma progression, MITF and the MAPK/ERK pathway, which appears more complex than previously anticipated.
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- 2021
23. Gene expression signature associated with BRAF mutations in human primary cutaneous melanomas
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Kannengiesser, Caroline, Spatz, Alain, Michiels, Stefan, Eychène, Alain, Dessen, Philippe, Lazar, Vladimir, Winnepenninckx, Véronique, Lesueur, Fabienne, Druillennec, Sabine, Robert, Caroline, van den Oord, Joost J., Sarasin, Alain, and Bressac-de Paillerets, Brigitte
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- 2008
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24. In Vivo Medulloblastoma Modeling
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Alain Eychène, Chloe Foray, Liliana Mirabal-Ortega, Magalie Larcher, Bertrand Duvillié, Morgane Morabito, Celio Pouponnot, Signalisation, radiobiologie et cancer, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Pouponnot, Celio
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Medulloblastoma ,0303 health sciences ,cerebellum ,business.industry ,orthotopic grafting ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,medicine.disease ,animal models ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,In vivo ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,cerebellar progenitors ,Patient-derived xenograft (PDX) ,business ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology - Abstract
International audience
- Published
- 2020
25. Alternative Splicing in Oncogenic Kinases: From Physiological Functions to Cancer
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Sabine Druillennec, Coralie Dorard, and Alain Eychène
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Genetics ,QH426-470 ,Biochemistry ,QD415-436 - Abstract
Among the 518 protein kinases encoded by the human kinome, several of them act as oncoproteins in human cancers. Like other eukaryotic genes, oncogenes encoding protein kinases are frequently subjected to alternative splicing in coding as well as noncoding sequences. In the present paper, we will illustrate how alternative splicing can significantly impact on the physiological functions of oncogenic protein kinases, as demonstrated by mouse genetic model studies. This includes examples of membrane-bound tyrosine kinases receptors (FGFR2, Ret, TrkB, ErbB4, and VEGFR) as well as cytosolic protein kinases (B-Raf). We will further discuss how regular alternative splicing events of these kinases are in some instances implicated in oncogenic processes during tumor progression (FGFR, TrkB, ErbB2, Abl, and AuroraA). Finally, we will present typical examples of aberrant splicing responsible for the deregulation of oncogenic kinases activity in cancers (AuroraB, Jak2, Kit, Met, and Ron).
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- 2012
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26. Cell context reveals a dual role for Maf in oncogenesis
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Pouponnot, C, Sii-Felice, K, Hmitou, I, Rocques, N, Lecoin, L, Druillennec, S, Felder-Schmittbuhl, M-P, and Eychène, A
- Published
- 2006
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27. B-raf alternative splicing is dispensable for development but required for learning and memory associated with the hippocampus in the adult mouse.
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Agathe Valluet, Isabelle Hmitou, Sabrina Davis, Sabine Druillennec, Magalie Larcher, Serge Laroche, and Alain Eychène
- Subjects
Medicine ,Science - Abstract
The B-raf proto-oncogene exerts essential functions during development and adulthood. It is required for various processes, such as placental development, postnatal nervous system myelination and adult learning and memory. The mouse B-raf gene encodes several isoforms resulting from alternative splicing of exons 8b and 9b located in the hinge region upstream of the kinase domain. These alternative sequences modulate the biochemical and biological properties of B-Raf proteins. To gain insight into the physiological importance of B-raf alternative splicing, we generated two conditional knockout mice of exons 8b and 9b. Homozygous animals with a constitutive deletion of either exon are healthy and fertile, and survive up to 18 months without any visible abnormalities, demonstrating that alternative splicing is not essential for embryonic development and brain myelination. However, behavioural analyses revealed that expression of exon 9b-containing isoforms is required for B-Raf function in hippocampal-dependent learning and memory. In contrast, mice mutated on exon 8b are not impaired in this function. Interestingly, our results suggest that exon 8b is present only in eutherians and its splicing is differentially regulated among species.
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- 2010
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28. Interplay Between Diabetes and Pancreatic Ductal Adenocarcinoma and Insulinoma: The Role of Aging, Genetic Factors, and Obesity
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Duvillié, Bertrand, primary, Kourdoughli, Rayane, additional, Druillennec, Sabine, additional, Eychène, Alain, additional, and Pouponnot, Celio, additional
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- 2020
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29. MafA Transcription Factor Identifies the Early Ret-Expressing Sensory Neurons
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Lecoin, Laure, Rocques, Nathalie, El-Yakoubi, Warif, Ben Achour, Sarrah, Larcher, Magalie, Pouponnot, Celio, and Eychène, Alain
- Published
- 2010
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30. An autocrine ActivinB mechanism drives TGFβ/Activin signaling in Group 3 medulloblastoma
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Alessandro Raso, Alain Eychène, Antoine Forget, Michael D. Taylor, Morgane Morabito, Magalie Larcher, Franck Bourdeaut, Florence M.G. Cavalli, Liliana Mirabal-Ortega, Olivier Delattre, Chloe Foray, Abel Debalkew, François Doz, Julien Masliah-Planchon, Sophie Leboucher, Celio Pouponnot, Alexandra Garancher, Mamy Andrianteranagna, Stéphanie Puget, Sabine Druillennec, Olivier Ayrault, Department of Anatomy and Cell Biology [Montréal], McGill University, Signalisation normale et pathologique de l'embryon aux thérapies innovante des cancers, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Bioinformatique (CBIO), MINES ParisTech - École nationale supérieure des mines de Paris-PSL Research University (PSL), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), PSL Research University (PSL), Institut Curie, Université Paris Sud Orsay, Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Signalisation cellulaire et neurobiologie (SNC), McGill University = Université McGill [Montréal, Canada], Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), Institut Curie [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Subjects
0301 basic medicine ,Cerebellum ,Medicine (General) ,medicine.medical_treatment ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Apoptosis ,Smad2 Protein ,QH426-470 ,0302 clinical medicine ,Transforming Growth Factor beta ,Phosphorylation ,Receptor ,Cancer ,Inhibin-beta Subunits ,activin ,Articles ,3. Good health ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,Autocrine Communication ,medicine.anatomical_structure ,TGFbeta ,Quinolines ,Molecular Medicine ,Female ,Signal Transduction ,Mice, Nude ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Antineoplastic Agents ,medulloblastoma ,Article ,TGFbeta Subject Category Cancer ,Transforming Growth Factor beta1 ,03 medical and health sciences ,R5-920 ,Transforming Growth Factor beta3 ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Cell Line, Tumor ,medicine ,Genetics ,Galunisertib ,Animals ,Humans ,Smad3 Protein ,Autocrine signalling ,Cerebellar Neoplasms ,Cell Proliferation ,Medulloblastoma ,Chemotherapy ,business.industry ,Mechanism (biology) ,Membrane Proteins ,medicine.disease ,Xenograft Model Antitumor Assays ,Radiation therapy ,030104 developmental biology ,Cancer research ,Pyrazoles ,business ,030217 neurology & neurosurgery ,Smad2 ,Smad3 - Abstract
International audience; Medulloblastoma (MB) is a pediatric tumor of the cerebellum divided into four groups. Group 3 is of bad prognosis and remains poorly characterized. While the current treatment involving surgery, radiotherapy, and chemotherapy often fails, no alternative therapy is yet available. Few recurrent genomic alterations that can be therapeutically targeted have been identified. Amplifications of receptors of the TGFb/Activin pathway occur at very low frequency in Group 3 MB. However, neither their functional relevance nor activation of the downstream signaling pathway has been studied. We showed that this pathway is activated in Group 3 MB with some samples showing a very strong activation. Beside genetic alterations, we demonstrated that an ActivinB autocrine stimulation is responsible for pathway activation in a subset of Group 3 MB characterized by high PMEPA1 levels. Importantly, Galunisertib, a kinase inhibitor of the cognate receptors currently tested in clinical trials for Glioblastoma patients, showed efficacy on orthotopically grafted MB-PDX. Our data demonstrate that the TGFb/Activin pathway is active in a subset of Group 3 MB and can be therapeutically targeted.
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- 2019
31. Vasoactive intestinal peptide-induced neurite remodeling in human neuroblastoma SH-SY5Y cells implicates the Cdc42 GTPase and is independent of Ras-ERK pathway
- Author
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Alleaume, Céline, Eychène, Alain, Harnois, Thomas, Bourmeyster, Nicolas, Constantin, Bruno, Caigneaux, Evelyne, Muller, Jean-Marc, and Philippe, Michel
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- 2004
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32. Translational control of tumor immune escape via the eIF4F-STAT1-PD-L1 axis in melanoma
- Author
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Alain Eychène, Laurent Désaubry, Michael Cerezo, Alexander M.M. Eggermont, Jean-Yves Scoazec, Stéphan Vagner, Nahum Sonenberg, Isabelle Girault, Sandrine Agoussi, Sylvain Martineau, Julien Adam, C. Libenciuc, Shensi Shen, Emilie Routier, Ramdane Guemiri, Charlène Estrada, Hélène Malka-Mahieu, Caroline Robert, Séverine Roy, Delphine Allard, Sabine Druillennec, Caroline Welsch, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Stress génotoxiques et cancer, Université Paris-Sud - Paris 11 (UP11)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Substances naturelles/chimie moléculaire, Université Louis Pasteur - Strasbourg I-Ecole européenne de chimie, polymères et matériaux [Strasbourg]-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Department of Biochemistry, Hôpital Lapeyronie, Département de biologie et pathologie médicales [Gustave Roussy], and Service de dermatologie
- Subjects
0301 basic medicine ,drug effects ,immunology ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Aucun ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,antagonists & inhibitors ,genetics ,therapeutic use ,General Biochemistry, Genetics and Molecular Biology ,B7-H1 Antigen ,03 medical and health sciences ,Interferon-gamma ,Mice ,Eukaryotic translation ,Downregulation and upregulation ,Cell Line, Tumor ,medicine ,Animals ,Humans ,STAT1 ,Transcription factor ,Melanoma ,ComputingMilieux_MISCELLANEOUS ,Messenger RNA ,biology ,Chemistry ,General Medicine ,Immunotherapy ,3. Good health ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,STAT1 Transcription Factor ,Eukaryotic Initiation Factor-4F ,eIF4A ,Protein Biosynthesis ,biology.protein ,STAT protein ,Cancer research ,Tumor Escape ,pathology ,therapy ,Signal Transduction - Abstract
Preventing the immune escape of tumor cells by blocking inhibitory checkpoints, such as the interaction between programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) receptor, is a powerful anticancer approach. However, many patients do not respond to checkpoint blockade. Tumor PD-L1 expression is a potential efficacy biomarker, but the complex mechanisms underlying its regulation are not completely understood. Here, we show that the eukaryotic translation initiation complex, eIF4F, which binds the 5' cap of mRNAs, regulates the surface expression of interferon-γ-induced PD-L1 on cancer cells by regulating translation of the mRNA encoding the signal transducer and activator of transcription 1 (STAT1) transcription factor. eIF4F complex formation correlates with response to immunotherapy in human melanoma. Pharmacological inhibition of eIF4A, the RNA helicase component of eIF4F, elicits powerful antitumor immune-mediated effects via PD-L1 downregulation. Thus, eIF4A inhibitors, in development as anticancer drugs, may also act as cancer immunotherapies. journal article research support, non-u.s. gov't 2018 12 2018 10 29 imported
- Published
- 2018
33. NRL and CRX Define Photoreceptor Identity and Reveal Subgroup-Specific Dependencies in Medulloblastoma
- Author
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Sabine Druillennec, Wilfrid Richer, Charles Y. Lin, Nadine El Tannir El Tayara, Robert J. Wechsler-Reya, Catherine Miquel, Morgane Morabito, Andreas Volk, Paul A. Northcott, François Doz, Stéphanie Puget, Olivier Ayrault, Olivier Delattre, Celio Pouponnot, Nathalie Rocques, Sophie Leboucher, Fanny Dupuy, Kyle S. Smith, Alexandra Garancher, Pascale Varlet, Laure Bihannic, Christine Walczak, Magalie Larcher, Alain Eychène, Nirmitha I. Herath, Franck Bourdeaut, Christine Haberler, Signalisation normale et pathologique de l'embryon aux thérapies innovante des cancers, Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Anatomy and Cell Biology [Montréal], McGill University, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie de l'Ecole polytechnique (BIOC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Signalisation cellulaire et neurobiologie (SNC), University of Alaska [Fairbanks] (UAF), Service de Neuropathologie [Sainte-Anne], Hôpital Sainte-Anne, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), PRES Sorbonne Paris Cité, Institut Curie, Unité de Génétique Somatique, Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), McGill University = Université McGill [Montréal, Canada], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Curie [Paris]
- Subjects
0301 basic medicine ,Cancer Research ,Lineage (genetic) ,genetic structures ,Transcription, Genetic ,Mice, Nude ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Retina ,Article ,03 medical and health sciences ,medicine ,Animals ,Humans ,Cerebellar Neoplasms ,Eye Proteins ,Transcription factor ,Gene ,ComputingMilieux_MISCELLANEOUS ,Medulloblastoma ,Homeodomain Proteins ,Cancer ,Cell Differentiation ,medicine.disease ,Phenotype ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Basic-Leucine Zipper Transcription Factors ,Oncology ,Cancer cell ,Trans-Activators ,sense organs ,Neuroscience - Abstract
Cancer cells often express differentiation programs unrelated to their tissue of origin, although the contribution of these aberrant phenotypes to malignancy is poorly understood. An aggressive subgroup of medulloblastoma, a malignant pediatric brain tumor of the cerebellum, expresses a photoreceptor differentiation program normally expressed in the retina. We establish that two photoreceptor-specific transcription factors, NRL and CRX, are master regulators of this program and are required for tumor maintenance in this subgroup. Beyond photoreceptor lineage genes, we identify BCL-XL as a key transcriptional target of NRL and provide evidence substantiating anti-BCL therapy as a rational treatment opportunity for select MB patients. Our results highlight the utility of studying aberrant differentiation programs in cancer and their potential as selective therapeutic vulnerabilities.
- Published
- 2018
34. An autocrine ActivinB mechanism drives TGF β/Activin signaling in Group 3 medulloblastoma
- Author
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Morabito, Morgane, primary, Larcher, Magalie, additional, Cavalli, Florence MG, additional, Foray, Chloé, additional, Forget, Antoine, additional, Mirabal‐Ortega, Liliana, additional, Andrianteranagna, Mamy, additional, Druillennec, Sabine, additional, Garancher, Alexandra, additional, Masliah‐Planchon, Julien, additional, Leboucher, Sophie, additional, Debalkew, Abel, additional, Raso, Alessandro, additional, Delattre, Olivier, additional, Puget, Stéphanie, additional, Doz, François, additional, Taylor, Michael D, additional, Ayrault, Olivier, additional, Bourdeaut, Franck, additional, Eychène, Alain, additional, and Pouponnot, Celio, additional
- Published
- 2019
- Full Text
- View/download PDF
35. MEDU-24. INSTRUMENTAL ROLE OF THE PHOTORECEPTOR PROGRAM IN GROUP 3 MEDULLOBLASTOMA THROUGH THE TRANSCRIPTION FACTOR NRL
- Author
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Alain Eychène, Paul A. Northcott, Magalie Larcher, Stéphanie Puget, Morgane Morabito, Franck Bourdeaut, Olivier Ayrault, Robert J. Wechsler-Reya, Catherine Miquel, Charles Y. Lin, Celio Pouponnot, Alexandra Garancher, Christine Habeler, and Nathalie Rocques
- Subjects
Medulloblastoma ,Cancer Research ,Abstracts ,Oncology ,genetic structures ,business.industry ,Cancer research ,Medicine ,Neurology (clinical) ,sense organs ,business ,medicine.disease ,Transcription factor - Abstract
Medulloblastoma (MB) is the most common malignant brain tumor of childhood arising in the cerebellum. Although multimodal treatments have significantly increased the survival, 20–30% of patients remain incurable. Most of them belong to a poorly characterized MB subgroup, called group3, which expresses a retina photoreceptor-specific differentiation program. Cancer cells often express such differentiation programs unrelated to their tissue of origin. They likely result from cancer cell plasticity but are usually not thought to contribute to cancer progression. Accordingly, the functional relevance of this aberrant differentiation program to MB remains unknown. By analyzing group3 enhancers (Enh) and super-enhancers (SE), we identified key interconnected transcription factors of this subgroup, Among those, two lineage restricted transcription factors, NRL and CRX, are known to play key roles during retina development and in particular for photoreceptor specification. We identified a list of genes harboring a co-occurrence of NRL and CRX binding sites within Enh/SE, and displaying higher expression in group3. Interestingly, photoreceptors genes are enriched among this list. This analysis showed that NRL and CRX are important players in group3 MB and control the photoreceptor differentiation program. By loss-of-function experiments in cell lines and PDXs, we showed that NRL and CRX are absolutely required for MB growth in vitro and in vivo upon orthotopic grafting. We then confirmed that NRL controls the expression of photoreceptor genes in group3 MB and established that it protects MB from apoptosis. By ChIP experiments we identified one of its key target genes in this process: the anti-apoptotic BCL-XL gene. We confirmed its key role downstream of NRL by rescue experiments. Importantly, we established the potential of anti-BCL therapies in MB. In conclusion, we showed that the photoreceptor program is instrumental to MB through NRL and CRX and that the anti-BCL therapies could represent an alternative therapeutic strategy.
- Published
- 2017
36. RAF proteins exert both specific and compensatory functions during tumour progression of NRAS-driven melanoma
- Author
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Lionel Larue, Jessy Leloup, Manuela Baccarini, Friedrich Beermann, Celio Pouponnot, Alexandra Garancher, Charlène Estrada, Céline Barbotin, Magalie Larcher, Coralie Dorard, Sabine Druillennec, and Alain Eychène
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Neuroblastoma RAS viral oncogene homolog ,Proto-Oncogene Proteins B-raf ,MAP Kinase Signaling System ,Science ,Transgene ,General Physics and Astronomy ,Mice, Transgenic ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Benign tumours ,Article ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Gene ,neoplasms ,Melanoma ,Monomeric GTP-Binding Proteins ,Mice, Knockout ,Multidisciplinary ,Effector ,Oncogenes ,General Chemistry ,medicine.disease ,digestive system diseases ,Mice, Inbred C57BL ,Proto-Oncogene Proteins c-raf ,030104 developmental biology ,Cell culture ,Cancer research ,Disease Progression ,ras Proteins - Abstract
NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically, CRAF but not BRAF was shown to be critical for various RAS-driven cancers, raising the question of the role of RAF proteins in NRAS-induced melanoma. Here, using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we investigate their contribution in tumour progression, from the onset of benign tumours to malignant tumour maintenance. We show that BRAF expression is required for ERK activation and nevi development, demonstrating a critical role in the early stages of NRAS-driven melanoma. After melanoma formation, single Braf or Craf ablation is not sufficient to block tumour growth, showing redundant functions for RAF kinases. Finally, proliferation of resistant cells emerging in the absence of BRAF and CRAF remains dependent on ARAF-mediated ERK activation. These results reveal specific and compensatory functions for BRAF and CRAF and highlight an addiction to RAF signalling in NRAS-driven melanoma., The melanoma-driver mutations in NRAS and BRAF are mutually exclusive but the contribution of RAF signalling downstream of NRAS remains to be clarified. Here, using mouse models, the authors show specific roles of each member of the RAF family at different stages of melanomagenesis.
- Published
- 2017
37. NRL and CRX Define Photoreceptor Identity and Reveal Subgroup-Specific Dependencies in Medulloblastoma
- Author
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Garancher, Alexandra, primary, Lin, Charles Y., additional, Morabito, Morgane, additional, Richer, Wilfrid, additional, Rocques, Nathalie, additional, Larcher, Magalie, additional, Bihannic, Laure, additional, Smith, Kyle, additional, Miquel, Catherine, additional, Leboucher, Sophie, additional, Herath, Nirmitha I., additional, Dupuy, Fanny, additional, Varlet, Pascale, additional, Haberler, Christine, additional, Walczak, Christine, additional, El Tayara, Nadine, additional, Volk, Andreas, additional, Puget, Stéphanie, additional, Doz, François, additional, Delattre, Olivier, additional, Druillennec, Sabine, additional, Ayrault, Olivier, additional, Wechsler-Reya, Robert J., additional, Eychène, Alain, additional, Bourdeaut, Franck, additional, Northcott, Paul A., additional, and Pouponnot, Celio, additional
- Published
- 2018
- Full Text
- View/download PDF
38. Cascadas de umbrales en un sistema agroforestal con café frente a disturbios del cambio global
- Author
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Eychène, Coline, Fallot, Abigaïl, Brenes, Cristian, Sepulveda, Claudia, Gestion des ressources renouvelables et environnement (UPR GREEN), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Grupo Cambio Climático y Cuencas del Centro Agronómico Tropical de Investigación y Enseñanza (CATIE-CCC), Centro Agronómico Tropical de Investigación y Enseñanza, Centro Agronómico Tropical de Investigación y Enseñanza - Tropical Agricultural Research and Higher Education Center (CATIE), Gestion des ressources renouvelables et environnement (Cirad-Es-UPR 47 GREEN), Département Environnements et Sociétés (Cirad-ES), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Centro Agronómico Tropical de Investigación y Enseñanza (CATIE), and CATIE
- Subjects
dinámicas socio-ecológicas ,P40 - Météorologie et climatologie ,F08 - Systèmes et modes de culture ,inter-escalas ,[SHS.ENVIR]Humanities and Social Sciences/Environmental studies ,E14 - Economie et politique du développement ,uso del suelo ,agroforestería ,irreversibilidad ,K10 - Production forestière ,P36 - Erosion, conservation et récupération des sols - Abstract
International audience; Climate change threats for territories where agroforestry prevails include land use changes that seem more irreversible than before, between coffee and sugarcane according to their respective price fluctuations. To understand the mechanisms driving coffee withdrawal and assess its level of irreversibility, we analyze dynamics in the Balaica subcorridor of the Costa Rican biological corridor CBVCT (Corredor Biológico Volcánico Central -Talamanca). Considering land use changes from shade coffee plantations to pastures or sugarcane fields, the instructions of the Resilience Assessment Workbook from the Resilience Alliance were applied so as to represent threshold cascades. With local experts of different disciplines, we investigate how economic, ecological and social phenomena interlink at the three scales of the landscape, its farming plot and the country. Two threshold cascades result from this investigation: from coffee to sugarcane and from coffee to pasture. In each case, they represent a set of hypotheses on how phenomenon of different kinds can succeed one another, leading to irreversible changes impeding balancing effects to take place for each phenomenon, for instance price adjustments or soil restoration.; Las amenazas del cambio climático para los territorios donde prevale la agroforestería, incluyen cambios de uso del suelo más irreversibles que los que se conocieron hasta ahora entre cultivos de café y de caña de azúcar según fluctuaciones de precios respectivos. Para entender los mecanismos rigiendo el abandono del café y evaluar su grado de irreversibilidad, analizamos las dinámicas en el subcorredor Balalaica del Corredor Biológico Volcánico Central -Talamanca (CBVCT) en Costa Rica. Considerando los cambios de cafetales bajo sombra a pastos o a cañales, aplicamos las instrucciones de la guía Resilience Assessment de la Resilience Alliance para la construcción de una cascada de umbrales. Investigamos con expertos locales de diferentes disciplinas, cómo se vinculan fenómenos económicos, ecológicos y sociales a las tres escala del territorio, de sus parcelas y del país. Los resultados consisten en dos cascadas de umbrales, de café à caña y de café a pasto. Representan en cada caso un conjunto de hipótesis sobre la posible sucesión de fenómenos de diferentes naturalezas, que lleva a cambios irreversibles por no poder contar con los efectos de reequilibrio que ocurren de forma separada, por ejemplo ajustes de precio en lo económico o restauración de suelos abandonados en lo ecológico.
- Published
- 2016
39. B-Raf and C-Raf Are Required for Melanocyte Stem Cell Self-Maintenance
- Author
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Sabine Druillennec, Manuela Baccarini, Celio Pouponnot, Alain Eychène, Lionel Larue, Anne H. Monsoro-Burq, Céline Barbotin, Agathe Valluet, Magalie Larcher, Coralie Dorard, Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulations cellulaires et oncogenèse (RCO), and Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Proto-Oncogene Proteins B-raf ,medicine.medical_specialty ,Lineage (genetic) ,[SDV]Life Sciences [q-bio] ,Xenopus ,Biology ,Melanocyte ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Cell Lineage ,c-Raf ,Extracellular Signal-Regulated MAP Kinases ,lcsh:QH301-705.5 ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Stem Cell Factor ,Kinase ,Melanoma ,Stem Cells ,Mesenchymal stem cell ,Cell Differentiation ,medicine.disease ,Cell biology ,Proto-Oncogene Proteins c-raf ,Proto-Oncogene Proteins c-kit ,Endocrinology ,medicine.anatomical_structure ,lcsh:Biology (General) ,Knockout mouse ,Melanocytes ,Stem cell ,Hair Follicle ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
International audience; B-Raf and C-Raf kinases have emerged as critical players in melanoma. However, little is known about their role during development and homeostasis of the melanocyte lineage. Here, we report that knockout of B-raf and C-raf genes in this lineage results in normal pigmentation at birth with no defect in migration, proliferation, or differentiation of melanoblasts in mouse hair follicles. In contrast, the double raf knockout mice displayed hair graying resulting from a defect in cell-cycle entry of melanocyte stem cells (MSCs) and their subsequent depletion in the hair follicle bulge. Therefore, Raf signaling is dispensable for early melanocyte lineage development, but necessary for MSC maintenance.
- Published
- 2012
40. Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1
- Author
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Alexander M.M. Eggermont, Jean Philippe Arnault, Sabine Druillennec, Nyam Kamsu-Kom, Alain Spatz, Gorana Tomasic, Nicolas Dumaz, Caroline Robert, Janine Wechsler, Emilie Hollville, Alain Eychène, Stéphan Vagner, Jocelyne André, Christine Mateus, Bernard Escudier, Alain Sarasin, Jean-Charles Soria, Magalie Larcher, Lise Boussemart, Ludovic Lacroix, and David Malka
- Subjects
Keratinocytes ,Male ,Neuroblastoma RAS viral oncogene homolog ,MAPK/ERK pathway ,Cancer Research ,Pathology ,Skin Neoplasms ,Pyridines ,Receptor, Transforming Growth Factor-beta Type I ,Neoplasms ,Cells, Cultured ,Skin ,Benzenesulfonates ,Middle Aged ,Sorafenib ,medicine.anatomical_structure ,Oncology ,Carcinoma, Squamous Cell ,Female ,raf Kinases ,Keratinocyte ,Signal Transduction ,medicine.drug ,Adult ,Niacinamide ,medicine.medical_specialty ,Ultraviolet Rays ,Blotting, Western ,Antineoplastic Agents ,Protein Serine-Threonine Kinases ,Biology ,Proto-Oncogene Proteins p21(ras) ,In vivo ,Biomarkers, Tumor ,medicine ,Humans ,PTEN ,HRAS ,neoplasms ,Aged ,Phenylurea Compounds ,Cancer ,medicine.disease ,digestive system diseases ,Mutation ,ras Proteins ,Cancer research ,biology.protein ,Tumor Suppressor Protein p53 ,Receptors, Transforming Growth Factor beta - Abstract
Purpose: The emergence of skin tumors in patients treated with sorafenib or with more recent BRAF inhibitors is an intriguing and potentially serious event. We carried out a clinical, pathologic, and molecular study of skin lesions occurring in patients receiving sorafenib. Experimental Design: Thirty-one skin lesions from patients receiving sorafenib were characterized clinically and pathologically. DNA extracted from the lesions was screened for mutation hot spots of HRAS, NRAS, KiRAS, TP53, EGFR, BRAF, AKT1, PI3KCA, TGFBR1, and PTEN. Biological effect of sorafenib was studied in vivo in normal skin specimen and in vitro on cultured keratinocytes. Results: We observed a continuous spectrum of lesions: from benign to more inflammatory and proliferative lesions, all seemingly initiated in the hair follicles. Eight oncogenic HRAS, TGFBR1, and TP53 mutations were found in 2 benign lesions, 3 keratoacanthomas (KA) and 3 KA-like squamous cell carcinoma (SCC). Six of them correspond to the typical UV signature. Treatment with sorafenib led to an increased keratinocyte proliferation and a tendency toward increased mitogen-activated protein kinase (MAPK) pathway activation in normal skin. Sorafenib induced BRAF–CRAF dimerization in cultured keratinocytes and activated CRAF with a dose-dependent effect on MAP-kinase pathway activation and on keratinocyte proliferation. Conclusion: Sorafenib induces keratinocyte proliferation in vivo and a time- and dose-dependent activation of the MAP kinase pathway in vitro. It is associated with a spectrum of lesions ranging from benign follicular cystic lesions to KA-like SCC. Additional and potentially preexisting somatic genetic events, like UV-induced mutations, might influence the evolution of benign lesions to more proliferative and malignant tumors. Clin Cancer Res; 18(1); 263–72. ©2011 AACR.
- Published
- 2012
41. A new MAFia in cancer
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Nathalie Rocques, Celio Pouponnot, and Alain Eychène
- Subjects
Genetics ,Regulation of gene expression ,Maf Transcription Factors, Large ,Applied Mathematics ,General Mathematics ,Cell ,Cancer ,Biology ,medicine.disease ,Models, Biological ,Cell biology ,Transformation (genetics) ,AP-1 transcription factor ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,Gene Expression Regulation ,Stroma ,Neoplasms ,Maf Transcription Factors ,medicine ,Humans ,Genes, Tumor Suppressor ,RNA Processing, Post-Transcriptional ,Multiple Myeloma ,Gene - Abstract
Like JUN and FOS, the Maf transcription factors belong to the AP1 family. Besides their established role in human cancer--overexpression of the large Maf genes promotes the development of multiple myeloma--they can display tumour suppressor-like activity in specific cellular contexts, which is compatible with their physiological role in terminal differentiation. However, their oncogenic activity relies mostly on the acquisition of new biological functions relevant to cell transformation, the most striking characteristic of Maf oncoproteins being their ability to enhance pathological interactions between tumour cells and the stroma.
- Published
- 2008
42. NRAS-driven melanoma: A RAF can hide another
- Author
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Druillennec, Sabine, primary, Pouponnot, Celio, additional, and Eychène, Alain, additional
- Published
- 2017
- Full Text
- View/download PDF
43. RAF proteins exert both specific and compensatory functions during tumour progression of NRAS-driven melanoma
- Author
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Dorard, Coralie, primary, Estrada, Charlène, additional, Barbotin, Céline, additional, Larcher, Magalie, additional, Garancher, Alexandra, additional, Leloup, Jessy, additional, Beermann, Friedrich, additional, Baccarini, Manuela, additional, Pouponnot, Celio, additional, Larue, Lionel, additional, Eychène, Alain, additional, and Druillennec, Sabine, additional
- Published
- 2017
- Full Text
- View/download PDF
44. GSK-3-Mediated Phosphorylation Enhances Maf-Transforming Activity
- Author
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Marie-Paule Felder-Schmittbuhl, Alain Eychène, Nancy Abou Zeid, Celio Pouponnot, Nathalie Rocques, Laure Lecoin, and Karine Sii-Felice
- Subjects
Maf Transcription Factors, Large ,Transcription, Genetic ,Molecular Sequence Data ,macromolecular substances ,Cell Line ,Phosphorylation cascade ,Glycogen Synthase Kinase 3 ,Phosphoserine ,Ubiquitin ,GSK-3 ,Maf Transcription Factors ,Chlorocebus aethiops ,Coactivator ,Animals ,Humans ,p300-CBP Transcription Factors ,Amino Acid Sequence ,Phosphorylation ,Molecular Biology ,Transcription factor ,biology ,Ubiquitination ,Cell Biology ,Cell cycle ,Rats ,Cell Transformation, Neoplastic ,Phosphothreonine ,COS Cells ,biology.protein ,Cancer research ,Chickens ,Protein Processing, Post-Translational - Abstract
The Maf oncoproteins are b-Zip transcription factors of the AP-1 superfamily. They are involved in developmental, metabolic, and tumorigenic processes. Maf proteins are overexpressed in about 50% of human multiple myelomas. Here, we show that Maf-transforming activity is controlled by GSK-3-dependent phosphorylation and that phosphorylation by GSK-3 can increase the oncogenic activity of a protein. Using microarray analysis, we identify a gene-expression subprogram regulated by GSK-3-mediated Maf phosphorylation involved in extracellular matrix remodeling and relevant to cancer progression. We also demonstrate that GSK-3 triggers MafA sequential phosphorylation on residues S61, T57, T53, and S49, inducing its ubiquitination and degradation. Paradoxically, this phosphorylation increases MafA-transcriptional activity through the recruitment of the coactivator P/CAF. We further demonstrate that P/CAF protects MafA from ubiquitination and degradation, suggesting that, upon the release of the coactivator complex, MafA becomes polyubiquitinated and degraded to allow the response to terminate.
- Published
- 2007
45. Differential Regulation of B-Raf Isoforms by Phosphorylation and AutoinhibitoryMechanisms
- Author
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Sabine Druillennec, Agathe Valluet, Carole Peyssonnaux, Alain Eychène, and Isabelle Hmitou
- Subjects
Proto-Oncogene Proteins B-raf ,Gene isoform ,Molecular Sequence Data ,MAP Kinase Kinase 1 ,Chick Embryo ,Biology ,medicine.disease_cause ,PC12 Cells ,Proto-Oncogene Mas ,Exon ,medicine ,Animals ,Humans ,Protein Isoforms ,Amino Acid Sequence ,Phosphorylation ,Molecular Biology ,Regulation of gene expression ,Mutation ,Sequence Homology, Amino Acid ,Alternative splicing ,Articles ,Cell Biology ,Rats ,Alternative Splicing ,Gene Expression Regulation ,Biochemistry ,Protein kinase domain ,Protein Binding - Abstract
The B-Raf proto-oncogene encodes several isoforms resulting from alternative splicing in the hinge region upstream of the kinase domain. The presence of exon 8b in the B2-Raf(8b) isoform and exon 9b in the B3-Raf(9b) isoform differentially regulates B-Raf by decreasing and increasing MEK activating and oncogenic activities, respectively. Using different cell systems, we investigated here the molecular basis of this regulation. We show that exons 8b and 9b interfere with the ability of the B-Raf N-terminal region to interact with and inhibit the C-terminal kinase domain, thus modulating the autoinhibition mechanism in an opposite manner. Exons 8b and 9b are flanked by two residues reported to down-regulate B-Raf activity upon phosphorylation. The S365A mutation increased the activity of all B-Raf isoforms, but the effect on B2-Raf(8b) was more pronounced. This was correlated to the high level of S365 phosphorylation in this isoform, whereas the B3-Raf(9b) isoform was poorly phosphorylated on this residue. In contrast, S429 was equally phosphorylated in all B-Raf isoforms, but the S429A mutation activated B2-Raf(8b), whereas it inhibited B3-Raf(9b). These results indicate that phosphorylation on both S365 and S429 participate in the differential regulation of B-Raf isoforms through distinct mechanisms. Finally, we show that autoinhibition and phosphorylation represent independent but convergent mechanisms accounting for B-Raf regulation by alternative splicing.
- Published
- 2007
46. PFKFB4 controls embryonic patterning via Akt signalling independently of glycolysis
- Author
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Caterina Pegoraro, Frédérique Maczkowiak, Alain Eychène, Celio Pouponnot, Ana Leonor Figueiredo, Anne H. Monsoro-Burq, Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, and Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
chemistry.chemical_classification ,Cell signaling ,Embryo, Nonmammalian ,Multidisciplinary ,Akt signalling ,Phosphofructokinase-2 ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,Ectoderm ,General Chemistry ,PFKFB4 ,Biology ,Embryonic Induction ,Embryonic stem cell ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,Oncogene Protein v-akt ,medicine.anatomical_structure ,Enzyme ,Biochemistry ,chemistry ,medicine ,Animals ,Glycolysis - Abstract
International audience; How metabolism regulators play roles during early development remains elusive. Here we show that PFKFB4 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4), a glycolysis regulator, is critical for controlling dorsal ectoderm global patterning in gastrulating frog embryos via a non-glycolytic function. PFKFB4 is required for dorsal ectoderm progenitors to proceed towards more specified fates including neural and non-neural ectoderm, neural crest or placodes. This function is mediated by Akt signalling, a major pathway that integrates cell homeostasis and survival parameters. Restoring Akt signalling rescues the loss of PFKFB4 in vivo. In contrast, glycolysis is not essential for frog development at this stage. Our study reveals the existence of a PFKFB4-Akt checkpoint that links cell homeostasis to the ability of progenitor cells to undergo differentiation, and uncovers glycolysis-independent functions of PFKFB4.
- Published
- 2014
47. Comparison of maf gene expression patterns during chick embryo development
- Author
-
Marie-Paule Felder-Schmittbuhl, Alain Eychène, Celio Pouponnot, Karine Sii-Felice, and Laure Lecoin
- Subjects
Limb Buds ,Chick Embryo ,In situ hybridization ,Biology ,Retina ,Mesoderm ,Proto-Oncogene Proteins ,Maf Transcription Factors ,Peripheral Nervous System ,Notochord ,Gene expression ,Genetics ,medicine ,Animals ,MafF Transcription Factor ,Blood islands ,Pancreas ,Molecular Biology ,In Situ Hybridization ,Gene Expression Profiling ,Neural tube ,Gene Expression Regulation, Developmental ,Nuclear Proteins ,Gastrula ,MafK Transcription Factor ,Molecular biology ,DNA-Binding Proteins ,Repressor Proteins ,Somite ,medicine.anatomical_structure ,Spinal Cord ,MAFB ,Proto-Oncogene Proteins c-maf ,Developmental Biology - Abstract
Maf proteins are basic-leucine zipper transcription factors belonging to the AP1 superfamily. Several developmental processes require Maf proteins yet, the redundancy or complementarity of their respective roles in common processes has been only partially investigated. We present for the first time a complete comparative analysis of maf gene expression patterns in vertebrates. Expression of c-maf, mafB/kreisler, mafA/L-maf, mafF, mafG and mafK was analyzed by whole-mount in situ hybridization within chick embryos and their extraembryonic tissues ranging from embryonic day (E) 1 to 7. We carefully examined the extent of overlap between distinct maf genes and report that the developing lens, kidney, pancreas and apoptotic zones of limb buds show sustained co-expression of large maf genes. Small maf genes also exhibit overlap, for example in the dermomyotome. We also describe so far unidentified sites of maf gene expression. mafA is found in the developing neural tube and dorsal root ganglia. c-maf hybridization is detected in the neuroretina, the notochord and the endothelium of extraembryonic blood vessels.
- Published
- 2004
48. sst2 Somatostatin Receptor Inhibits Cell Proliferation through Ras-, Rap1-, and B-Raf-dependent ERK2 Activation
- Author
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Alain Eychène, Jean-Pierre Estève, Nathalie Saint-Laurent, Lucien Pradayrol, Stéphane Pyronnet, Hicham Lahlou, and Christiane Susini
- Subjects
Proto-Oncogene Proteins B-raf ,endocrine system ,MAP Kinase Signaling System ,Cell Cycle Proteins ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,CHO Cells ,Protein tyrosine phosphatase ,Biology ,Models, Biological ,Biochemistry ,Receptor tyrosine kinase ,Mice ,Cricetinae ,Animals ,Insulin ,Receptors, Somatostatin ,Pancreas ,Molecular Biology ,Protein kinase B ,Mice, Knockout ,Mitogen-Activated Protein Kinase 1 ,Mitogen-Activated Protein Kinase 3 ,Akt/PKB signaling pathway ,Protein Tyrosine Phosphatase, Non-Receptor Type 6 ,Tumor Suppressor Proteins ,Intracellular Signaling Peptides and Proteins ,rap1 GTP-Binding Proteins ,JAK-STAT signaling pathway ,Cell Biology ,Cell biology ,Enzyme Activation ,Mice, Inbred C57BL ,Proto-Oncogene Proteins c-raf ,ras Proteins ,Cancer research ,biology.protein ,Mitogen-Activated Protein Kinases ,Protein Tyrosine Phosphatases ,Somatostatin ,Tyrosine kinase ,Cell Division ,Cyclin-Dependent Kinase Inhibitor p27 ,Platelet-derived growth factor receptor ,Proto-oncogene tyrosine-protein kinase Src - Abstract
The G protein-coupled sst2 somatostatin receptor is a critical negative regulator of cell proliferation. sstII prevents growth factor-induced cell proliferation through activation of the tyrosine phosphatase SHP-1 leading to induction of the cyclin-dependent kinase inhibitor p27Kip1. Here, we investigate the signaling molecules linking sst2 to p27Kip1. In Chinese hamster ovary-DG-44 cells stably expressing sst2 (CHO/sst2), the somatostatin analogue RC-160 transiently stimulates ERK2 activity and potentiates insulin-stimulated ERK2 activity. RC-160 also stimulates ERK2 activity in pancreatic acini isolated from normal mice, which endogenously express sst2, but has no effect in pancreatic acini derived from sst2 knock-out mice. RC-160-induced p27Kip1 up-regulation and inhibition of insulin-dependent cell proliferation are both prevented by pretreatment of CHO/sst2 cells with the MEK1/2 inhibitor PD98059. In addition, using dominant negative mutants, we show that sst2-mediated ERK2 stimulation is dependent on the pertussis toxin-sensitive Gi/o protein, the tyrosine kinase Src, both small G proteins Ras and Rap1, and the MEK kinase B-Raf but is independent of Raf-1. Phosphatidylinositol 3-kinase (PI3K) and both tyrosine phosphatases, SHP-1 and SHP-2, are required upstream of Ras and Rap1. Taken together, our results identify a novel mechanism whereby a Gi/o protein-coupled receptor inhibits cell proliferation by stimulating ERK signaling via a SHP-1-SHP-2-PI3K/Ras-Rap1/B-Raf/MEK pathway.
- Published
- 2003
49. Activated MAPK/ERK Kinase (MEK-1) Induces Transdifferentiation of Pigmented Epithelium into Neural Retina
- Author
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Alain Eychène, Anne Galy, Simon Saule, Bertrand Néron, and Nathalie Planque
- Subjects
MAPK/ERK pathway ,retina ,medicine.medical_specialty ,Blotting, Western ,Genetic Vectors ,MAP Kinase Kinase 1 ,embryo ,Chick Embryo ,Protein Serine-Threonine Kinases ,Biology ,Fibroblast growth factor ,pigment ,Internal medicine ,medicine ,Animals ,FGF ,Pigment Epithelium of Eye ,Molecular Biology ,Mitogen-Activated Protein Kinase Kinases ,Microphthalmia-Associated Transcription Factor ,integumentary system ,Neuroectoderm ,Transdifferentiation ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Raf ,Cell Biology ,Optic vesicle ,Microphthalmia-associated transcription factor ,MAPK ,eye diseases ,Cell biology ,DNA-Binding Proteins ,Enzyme Activation ,Phenotype ,Retroviridae ,Endocrinology ,microphthalmia ,Eye development ,Fibroblast Growth Factor 2 ,Ectopic expression ,sense organs ,signaling ,Cell Division ,Photoreceptor Cells, Vertebrate ,Transcription Factors ,Ras ,Developmental Biology - Abstract
During vertebrate eye development, the optic vesicle originating from the neuroectoderm is partitioned into a domain that will give rise to the neural retina (NR) and another that will give rise to the retinal pigmented epithelium (RPE). Previous studies have shown that ectopic expression of FGFs in the RPE induces RPE-to-NR transdifferentiation. Similarly, a naturally occurring mutation of the transcription factor Mitf in mouse resulted in the formation of a second neural retina in place of the dorsal RPE, but the putative signaling pathway linking FGF to Mitf regulation is presently unknown. In cultures of neural crest-derived melanocytes, the MAPK pathway was recently shown to target the Mitf transcription factor for ubiquitin-dependent proteolysis, resulting in a rapid degradation and downregulation. In the present study, we show that ectopic expression of a constitutively activated allele of MEK-1, the immediate upstream activator of the MAPK ERK, in chicken embryonic retina in ovo, induces transdifferentiation of the RPE into a neural-like epithelium that is correlated with a downregulation of Mitf expression in the presumptive RPE.
- Published
- 2002
50. NRAS-driven melanoma: A RAF can hide another
- Author
-
Alain Eychène, Celio Pouponnot, and Sabine Druillennec
- Subjects
0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,tumor ,Cancer Research ,Melanoma ,Biology ,CRAF ,medicine.disease ,ARAF ,BRAF ,resistance ,03 medical and health sciences ,030104 developmental biology ,melanoma ,Cancer research ,medicine ,Molecular Medicine ,human ,Author's View ,neoplasms ,mouse ,RAS - Abstract
Using mouse genetics, we recently showed that BRAF has a critical role in initiation of NRAS-driven melanoma that cannot be compensated by CRAF. In contrast, RAF proteins display compensatory functions in fully established tumors and ARAF can sustain proliferation in the absence of BRAF and CRAF, highlighting an addiction to RAF signaling in NRAS-driven melanoma.
- Published
- 2017
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