Descriptor: "MESH : Tumor Cells, Cultured" - Searchworks@Jio Institute Digital Library Search Results

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19 results on '"MESH : Tumor Cells, Cultured"'

1. Sex differences in the GSK3β-mediated survival of adherent leukemic progenitors

Author: Jessica Bertrand, Bernard Payrastre, N Gallay, Nathalie Vergnolle, Véronique Maguer-Satta, Mathieu Despeaux, Cécile Demur, Ezzeddine Bourogaa, S Joly, P Bonnevialle, F Louache, Claire Racaud-Sultan, ANDRA, Laboratoire d'Hématologie [Purpan], Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Equipe 11, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Physiopathologie Toulouse Purpan, Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut Claudius Regaud-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud
Subjects: Male, MESH : Aged, Antigens, CD34, MESH : Blotting, Western, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Glycogen Synthase Kinase 3, 0302 clinical medicine, MESH : Indoles, MESH : Tumor Cells, Cultured, GSK-3, Tumor Cells, Cultured, Protein Phosphatase 2, MESH : GTP-Binding Proteins, Cells, Cultured, MESH: Glycogen Synthase Kinase 3, MESH: Etoposide, Etoposide, MESH: Indoles, MESH : Maleimides, Aged, 80 and over, MESH : Cell Survival, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Protein Phosphatase 2, Neoplasm Proteins, MESH: Cell Survival, MESH: Young Adult, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, RNA Interference, MESH: Cells, Cultured, MESH : Protein Phosphatase 2, MESH : Glycogen Synthase Kinase 3, MESH: Antineoplastic Agents, Phytogenic, Blotting, Western, MESH : Young Adult, Receptors, Cell Surface, MESH: Cell Adhesion, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH: Sex Factors, Genetics, MESH: Blotting, Western, Humans, MESH : Middle Aged, MESH: Tumor Cells, Cultured, Progenitor cell, MESH : Aged, 80 and over, Clonogenic assay, education, Molecular Biology, Aged, MESH: Interleukin-3 Receptor alpha Subunit, MESH: Humans, Glycogen Synthase Kinase 3 beta, MESH : Hematopoietic Stem Cells, MESH : Humans, MESH : Leukemia, MESH: Adult, MESH: Antigens, CD34, Protein phosphatase 2, Hematopoietic Stem Cells, MESH: Neoplastic Stem Cells, Immunology, MESH: Female, MESH: Neoplasm Proteins, Cancer Research, Indoles, MESH : Receptors, Cell Surface, MESH : Interleukin-3 Receptor alpha Subunit, MESH : Antineoplastic Agents, Phytogenic, MESH: Hematopoietic Stem Cells, Maleimides, MESH: Aged, 80 and over, MESH : Female, MESH: Maleimides, MESH: Receptors, Cell Surface, MESH: Aged, Leukemia, Myeloid leukemia, MESH : Adult, Middle Aged, medicine.anatomical_structure, MESH : Antigens, CD34, Female, Stem cell, Adult, MESH: GTP-Binding Proteins, Cell Survival, MESH : Male, MESH : Sex Factors, MESH: RNA Interference, Population, Interleukin-3 Receptor alpha Subunit, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Etoposide, Biology, Receptors for Activated C Kinase, Young Adult, MESH : Neoplastic Stem Cells, Sex Factors, GTP-Binding Proteins, MESH: Leukemia, MESH : Cells, Cultured, Cell Adhesion, medicine, 030304 developmental biology, Antineoplastic Agents, Phytogenic, MESH: Male, MESH : Cell Adhesion, Cancer research, Bone marrow, MESH : RNA Interference
Abstract: International audience; Therapeutic resistance of acute myeloid leukemia stem cells, enriched in the CD34(+)38(-)123(+) progenitor population, is supported by extrinsic factors such as the bone marrow niche. Here, we report that when adherent onto fibronectin or osteoblast components, CD34(+)38(-)123(+) progenitors survive through an integrin-dependent activation of glycogen synthase kinase 3β (GSK3β) by serine 9-dephosphorylation. Strikingly, GSK3β-mediated survival was restricted to leukemic progenitors from female patients. GSK3β inhibition restored sensitivity to etoposide, and impaired the clonogenic capacities of adherent leukemic progenitors from female patients. In leukemic progenitors from female but not male patients, the scaffolding protein RACK1, activated downstream of α(5)β(1)-integrin engagement, was specifically upregulated and controlled GSK3β activation through the phosphatase protein phosphatase 2A (PP2A). In a mirrored manner, survival of adherent progenitors (CD34(+)38(-)) from male but not female healthy donors was partially dependent on this pathway. We conclude that the GSK3β-dependent survival pathway might be sex-specific in normal immature population and flip-flopped upon leukemogenesis. Taken together, our results strengthen GSK3β as a promising target for leukemic stem cell therapy and reveal gender differences as a new parameter in anti-leukemia therapy.
Published: 2011

2. miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers

Author: Khalil Arar, Christina Laurini, Michèle Sabbah, Laurent Vallar, Michèle Moes, Charles-Henri Lecellier, Evelyne Friederich, A. Le Bechec, Guillaume Vetter, Anne Saumet, Charles Theillet, Le Ster, Yves, Cytoskeleton and Cell Plasticity Lab, Université du Luxembourg (Uni.lu), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche Publique- Santé, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sigma-Aldrich - Evry GENEPOLE, Sigma-Aldrich, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the Fond National de la Recherche (FNR) du Luxembourg, (BIOSAN), the Fondation Luxembourgeoise Contre le Cancer, Human Frontier Science Program (RGP0058/2005), INSERM and CNRS, France. A. Saumet is a recipient of a fellowship from the Ministère de la Culture, de l'Enseignement Supérieur et de la Recherche, Luxembourg (BFR 08/046). M. Moes and A. Le Béchec are supported by AFR grants from the Fond National de la Recherche, Luxembourg., CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université du Luxembourg ( Uni.lu ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: SNAI1, Cancer Research, MESH : RNA, Messenger, MESH : Transcription Factors, MESH : Cell Dedifferentiation, Gene Expression, MESH : Breast Neoplasms, Biochemistry, biophysics & molecular biology [F05] [Life sciences], Validation Studies as Topic, MESH : RNA, Small Interfering, medicine.disease_cause, Bioinformatics, MESH : Neoplasm Invasiveness, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Metastasis, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH : Validation Studies as Topic, EMT/miR-661/ SNAI1/StarD10/Nectin-1/breast cancer cell invasion, MESH: RNA, Small Interfering, Tumor Cells, Cultured, MESH : Female, RNA, Small Interfering, Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant], Oligonucleotide Array Sequence Analysis, 0303 health sciences, EMT, MESH: Transcription Factors, MESH: Gene Expression Regulation, Neoplastic, MESH : Epithelial Cells, Gene Expression Regulation, Neoplastic, MESH : Oligonucleotide Array Sequence Analysis, MESH: Epithelial Cells, 030220 oncology & carcinogenesis, MESH: Cell Adhesion Molecules, Female, Breast disease, StarD10, Nectin-1, MESH: Gene Expression, MESH : Gene Expression Regulation, Neoplastic, Nectins, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MESH: Phosphoproteins, MESH : Cell Adhesion Molecules, MESH: Gene Expression Profiling, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, microRNA, Genetics, medicine, Humans, Gene silencing, Neoplasm Invasiveness, RNA, Messenger, MESH: Tumor Cells, Cultured, Epithelial–mesenchymal transition, Molecular Biology, MESH: RNA, Messenger, 030304 developmental biology, breast cancer cell invasion, MESH: Validation Studies as Topic, MESH: Humans, MESH : Gene Expression Profiling, Gene Expression Profiling, MESH : Humans, Cancer, Epithelial Cells, Mesenchymal Stem Cells, MESH: Neoplasm Invasiveness, Cell Dedifferentiation, Phosphoproteins, medicine.disease, MESH: Cell Dedifferentiation, miR-661, MESH : Gene Expression, MESH : MicroRNAs, MicroRNAs, Retraction Note, MESH: Mesenchymal Stem Cells, MESH: Oligonucleotide Array Sequence Analysis, Cancer research, Snail Family Transcription Factors, MESH : Phosphoproteins, MESH : Mesenchymal Stem Cells, Carcinogenesis, Cell Adhesion Molecules, MESH: MicroRNAs, MESH: Female, MESH: Breast Neoplasms, Transcription Factors
Abstract: 4; International audience; Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell-cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. Reexpression of Nectin-1 or StarD10 lacking the 3'-untranslated region counteracted SNAI1-induced invasion. Importantly, analysis of public transcriptomic data from a cohort of 295 well-characterized breast tumor specimen revealed that expression of StarD10 is highly associated with markers of luminal subtypes whereas its loss negatively correlated with the EMT-related, basal-like subtype. Collectively, our non-a priori approach revealed a nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome.
Published: 2010

3. Selective mRNA degradation by antisense oligonucleotide-2,5A chimeras: Involvement of RNase H and RNase L

Author: Anna Ubysz, Ian Robbins, Bernard Lebleu, Sylvie Vichier-Guerre, Robert W. Sobol, Guillaume Mitta, Bernard Rayner, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), LCBO-Laboratoire de Chimie Bio-organique, Université Montpellier 2 - Sciences et Techniques (UM2), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 2 - Sciences et Techniques ( UM2 ), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: MESH : Cell Line, MESH : Protein Biosynthesis, MESH : RNA, Messenger, MESH: Ribonuclease, Pancreatic, MESH : Ribonuclease, Pancreatic, MESH : Models, Biological, MESH : Ribonuclease H, Calf Thymus, Biochemistry, MESH: Nucleic Acid Hybridization, Mice, MESH: Oligonucleotides, Antisense, MESH : Tumor Cells, Cultured, Gene expression, Tumor Cells, Cultured, MESH: Animals, MESH: Ribonuclease H, Calf Thymus, 0303 health sciences, MESH: Spodoptera, biology, 030302 biochemistry & molecular biology, Nucleic Acid Hybridization, Translation (biology), General Medicine, MESH : Nucleic Acid Hybridization, 3. Good health, MESH: Protein Biosynthesis, Antisense oligonucleotides, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], RNase P, Ribonuclease H, Spodoptera, MESH : Spodoptera, Models, Biological, Cell Line, 03 medical and health sciences, MESH : Mice, Animals, Humans, MESH: Tumor Cells, Cultured, RNA, Messenger, [ SDV.OT ] Life Sciences [q-bio]/Other [q-bio.OT], RNase H, MESH: Mice, MESH: RNA, Messenger, 030304 developmental biology, MESH: Humans, Oligonucleotide, MESH : Humans, MESH : Oligonucleotides, Antisense, MESH: Models, Biological, RNA, Ribonuclease, Pancreatic, Oligonucleotides, Antisense, MESH: Cell Line, RNase MRP, Protein Biosynthesis, biology.protein, MESH : Animals
Abstract: Antisense oligonucleotides (ON) allow the specific control of gene expression and phosphorothioate derivatives are currently being evaluated for possible clinical applications. Numerous second generation ON analogues with improved pharmacological properties have been described. Most of them, however, do not recruit RNase H, which is known to increase ON potency by eliciting the specific degradation of the target RNA. Silverman, Torrence and colleagues, have conjugated 2.5 A to natural antisense ON and demonstrated the preferential cleavage of a target RNA in cell-free and intact cell experiments. We have established for the first time that RNase H-incompetent ON, viz, α-anomeric ON analogues, can be converted into sequence-specific nucleases upon conjugation to 2,5 A. The use of α-ON and β-ON-2,5 A chimeras has allowed us to delineate the part played by RNase H and RNase L in target RNA degradation and translation arrest. Finally, the present studies have revealed limitations which are encountered in the choice of a suitable target for such ON-2,5 A chimeras.
Published: 1998

4. A protocol to quantify mammary early common progenitors from long-term mammosphere culture

Author: Véronique Maguer-Satta, Emmanuel Delay, Elodie Bachelard-Cascales, Marion Chapellier, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Neoplasm Proteins, Time Factors, Cellular differentiation, Cell Culture Techniques, MESH : Aged, MESH : Receptors, Cell Surface, MESH : Blotting, Western, MESH : Interleukin-3 Receptor alpha Subunit, MESH : Antineoplastic Agents, Phytogenic, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Hematopoietic Stem Cells, Mice, 0302 clinical medicine, MESH: Aged, 80 and over, MESH : Indoles, MESH : Tumor Cells, Cultured, MESH : Female, MESH : GTP-Binding Proteins, MESH: Glycogen Synthase Kinase 3, MESH: Maleimides, MESH: Receptors, Cell Surface, MESH: Etoposide, MESH : Maleimides, MESH: Aged, MESH: Indoles, MESH : Cell Survival, 0303 health sciences, MESH: Middle Aged, Stem Cells, MESH: Protein Phosphatase 2, Cell Differentiation, General Medicine, MESH : Adult, Cell biology, MESH: Cell Survival, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH : Antigens, CD34, Stem cell, MESH: Cells, Cultured, Adult, MESH: GTP-Binding Proteins, MESH : Protein Phosphatase 2, MESH : Glycogen Synthase Kinase 3, MESH : Male, MESH : Sex Factors, MESH: RNA Interference, MESH: Antineoplastic Agents, Phytogenic, MESH : Young Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Etoposide, Biology, MESH: Cell Adhesion, Colony-Forming Units Assay, 03 medical and health sciences, MESH : Neoplasm Proteins, MESH : Neoplastic Stem Cells, MESH: Sex Factors, Spheroids, Cellular, MESH : Cells, Cultured, MESH: Leukemia, Animals, Humans, MESH: Blotting, Western, MESH : Middle Aged, MESH: Tumor Cells, Cultured, Progenitor cell, Mammary Glands, Human, MESH : Aged, 80 and over, 030304 developmental biology, Progenitor, MESH: Interleukin-3 Receptor alpha Subunit, MESH: Humans, MESH : Hematopoietic Stem Cells, Stem cell population, MESH : Humans, MESH : Leukemia, MESH: Adult, Cell Biology, MESH: Antigens, CD34, MESH: Neoplastic Stem Cells, MESH: Male, MESH : Cell Adhesion, Cell culture, Immunology, NIH 3T3 Cells, MESH : RNA Interference, MESH: Female, Developmental Biology
Abstract: International audience; Here we describe a protocol established in our laboratory to quantify early common progenitors/stem cells grown as spheres in non-adherent culture conditions. This protocol is based on the combination of two functional tests: the mammosphere assay to maintain and enrich early mammary progenitors/stem cells, and the epithelial colony-forming cells (E-CFC) assay to identify and quantify further differentiated epithelial progenitors. Primary spheres mainly contain progenitors and rare stem/early common progenitor cells while secondary and tertiary spheres contain progenitor cells derived from the early common progenitor/stem cell population maintained through passages and partially differentiated. Spheres are enzymatically and mechanically dissociated; the derived cells are subsequently plated on irradiated NIH-3T3 fibroblasts for further processing, as in the E-CFC assay. The principle of this assay is to quantify the number of epithelial colonies generated by cells present in the different sequential spheres. This assay has therefore been named ECP-DC, standing for Early Common Progenitor-Derived Colonies assay.
Published: 2012

5. Autocrine proliferative effects of hGH are maintained in primary cultures of human mammary carcinoma cells

Author: Jean Chiesa, Cécile M. Vouyovitch, Samia Gonzalez, Zhengsheng Wu, Pierre Mares, Hichem C. Mertani, Jean-Jacques Diaz, Gérard Morel, Peter E. Lobie, Tao Zhu, Catherine Ferrer, Cécile Arnould, Laboratoire de Cytogénétique, Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Equipe 8, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre de génétique et de physiologie moléculaire et cellulaire ( CGPhiMC ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Service de gynécologie obstétrique, Hôpital Universitaire Carémeau [Nîmes], Equipe 4, Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), The Liggins Institute and the National Research Centre for Growth and Development, University of Auckland [Auckland], Department of Molecular Medicine and Pathology, Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Carcinoma, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Cell, MESH : Aged, Stimulation, MESH : Breast Neoplasms, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Endocrinology, MESH: Aged, 80 and over, MESH : Tumor Cells, Cultured, Tumor Cells, Cultured, MESH: Human Growth Hormone, MESH : Cell Proliferation, MESH : Female, Receptor, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Chemistry, Human Growth Hormone, MESH : Carcinoma, Middle Aged, MESH : Adult, 3. Good health, Autocrine Communication, medicine.anatomical_structure, 030220 oncology & carcinogenesis, embryonic structures, Female, MESH: Membrane Proteins, MESH : Autocrine Communication, hormones, hormone substitutes, and hormone antagonists, Adult, medicine.medical_specialty, endocrine system, Context (language use), Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, MESH: Cell Proliferation, medicine, Humans, MESH : Middle Aged, MESH: Tumor Cells, Cultured, MESH : Human Growth Hormone, Autocrine signalling, MESH : Aged, 80 and over, 030304 developmental biology, Aged, Cell Proliferation, MESH: Humans, Biochemistry (medical), Carcinoma, MESH : Humans, Antagonist, Membrane Proteins, MESH: Adult, Epithelium, In vitro, MESH : Membrane Proteins, MESH: Autocrine Communication, MESH: Female, MESH: Breast Neoplasms
Abstract: International audience; CONTEXT: Empirical evidence suggests that autocrine human GH (hGH) may possess a proliferative and oncogenic role in human mammary carcinoma. However, this concept is largely derived from studies using cultured human mammary carcinoma cell (HMCC) lines. OBJECTIVE: We investigated the expression and functionality of hGH and the hGH receptor in isolated cultures of primary HMCC. Design: Epithelial cell adhesion molecule-positive primary HMCC were isolated from surgical biopsies of patients with mammary carcinoma and cultured in vitro. Expression of hGH and hGH receptor was determined by RT-PCR, immunofluorescence microscopy, and ELISA. The proliferative response of the cultured primary HMCC to hGH stimulation or hGH inhibition with a hGH antagonist was determined. RESULTS: One hundred percent of cultured primary HMCC expressed the hGH receptor, and 52% expressed hGH at the mRNA level. hGH-positive primary HMCC produced hGH protein within the cell and secreted hGH to the media. Both hGH-negative and hGH-positive HMCC responded to hGH stimulation with large increases in cell number. hGH-positive HMCC responded to inhibition of hGH by a hGH antagonist with a decrease in cell number, whereas hGH-negative HMCC did not. CONCLUSION: Primary HMCC proliferate in response to hGH, and the proliferation of hGH-positive HMCC is inhibited by hGH antagonism. Inhibition of hGH in patients with mammary carcinoma may therefore limit tumor growth.
Published: 2011

6. Accumulation of lactosylceramide and overexpression of a PSC833-resistant P-glycoprotein in multidrug-resistant human sarcoma cells

Author: Nassera Aouali, Lahcen Eddabra, Hassan El Btaouri, Claudie Madoulet, Hamid Morjani, Charles Dumontet, Sophie Malagarie-Cazenave, Equipe 14, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Onco-Pharmacologie ( LOP ), Université de Reims Champagne-Ardenne ( URCA ) -JE2428, Université de Reims Champagne-Ardenne ( URCA ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Onco-Pharmacologie (LOP), Université de Reims Champagne-Ardenne (URCA)-JE2428, and Université de Reims Champagne-Ardenne (URCA)
Subjects: Cancer Research, MESH : RNA, Messenger, MESH: Flow Cytometry, MESH : Blotting, Western, MESH : Lactosylceramides, MESH : P-Glycoprotein, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH: Reverse Transcriptase Polymerase Chain Reaction, Cyclosporin a, Tumor Cells, Cultured, polycyclic compounds, MESH : Cell Proliferation, Cytotoxic T cell, MESH: Cyclosporins, MESH: Antigens, CD, P-glycoprotein, 0303 health sciences, music.instrument, Antibiotics, Antineoplastic, biology, Reverse Transcriptase Polymerase Chain Reaction, MESH : Reverse Transcriptase Polymerase Chain Reaction, Sarcoma, General Medicine, Flow Cytometry, MESH: Drug Resistance, Neoplasm, Drug Resistance, Multiple, MESH : Antibiotics, Antineoplastic, 3. Good health, MESH : Drug Resistance, Neoplasm, Oncology, Biochemistry, 030220 oncology & carcinogenesis, MESH: Daunorubicin, medicine.drug, MESH: P-Glycoprotein, Daunorubicin, MESH : Flow Cytometry, Blotting, Western, Lactosylceramides, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cyclosporins, MESH : Sarcoma, MESH: Drug Resistance, Multiple, MESH: Doxorubicin, 03 medical and health sciences, Lactosylceramide, Antigens, CD, MESH: Cell Proliferation, medicine, MESH : Antigens, CD, MESH: Blotting, Western, Humans, MESH : Doxorubicin, Doxorubicin, MESH: Tumor Cells, Cultured, ATP Binding Cassette Transporter, Subfamily B, Member 1, RNA, Messenger, MESH : Cyclosporins, MESH: Antibiotics, Antineoplastic, MESH: Lactosylceramides, music, MESH: RNA, Messenger, 030304 developmental biology, Cell Proliferation, MESH: Humans, MESH : Humans, Molecular biology, Multiple drug resistance, Cell culture, Drug Resistance, Neoplasm, MESH: Sarcoma, biology.protein, MESH : Daunorubicin, MESH : Drug Resistance, Multiple
Abstract: International audience; The selection pressure for resistance to chemotherapy is accompanied by the enhanced expression of ABC proteins and increased cellular glycosphingolipid content. Thus, a possible connection between glycosphingolipid metabolism and ABC proteins in drug resistance has been suggested. In the present study, we established two human multidrug-resistant (MDR) cell lines derived from MESSA sarcoma cells by culturing with increasing concentrations of doxorubicin (DX5 cells) or doxorubicin together with cyclosporin A (GARF cells). Both resistant cell lines overexpressed the MDR1 gene and the wild-type P-glycoprotein at the same level. The cyclosporin derivative PSC833, a potent inhibitor of P-glycoprotein, sensitized DX5 but not GARF cells to the cytotoxic effects of daunorubicin. Moreover, PSC833 increased the nuclear accumulation of daunorubicin and the cellular accumulation of [3H]vinblastine in the DX5 but not in the GARF cells. The cellular incorporation of [3H]-cyclosporin A was lower in DX5 cells compared to MESSA and GARF cells, which incorporated the same level of [3H]-cyclosporin A. Sphingolipid analysis showed that the lactosylceramide level was 2.5- and 5-fold higher in DX5 and GARF cells, respectively, than in MESSA cells. Whereas the pharmacological inhibition of lactosylceramide synthesis was able to reverse only partially the resistance of GARF cells to daunorubicin without significant increase in nuclear accumulation of the drug, the same treatment before the co-treatment with PSC833 and daunorubicin increased the cytotoxic effect of daunorubicin and its nuclear accumulation. These data suggest a possible relationship between lactosylceramide levels and the resistance of P-glycoprotein to modulation by MDR modulators.
Published: 2011

7. CXCR7 is up-regulated in human and murine hepatocellular carcinoma and is specifically expressed by endothelial cells

Author: Bruno Turlin, Claire Piquet-Pellorce, Marie-Lise Lacombe, Michel Samson, J. Monnier, Annie L'Helgoualc'h, Nathalie Théret, Mathieu Boissan, Jessica Zucman-Rossi, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche Phytopharmacie et Médiateurs Chimiques (UPMC), Institut National de la Recherche Agronomique (INRA), CHU Pontchaillou [Rennes], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité de recherche Phytopharmacie et Médiateurs Chimiques ( UPMC ), Institut National de la Recherche Agronomique ( INRA ), Service d'anatomopathologie, Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (UMRS893), INSERM, Ministère de l’Education Nationale de la Recherche et de la Technologie, Région Bretagne, National French Society of Gastroenterology (SNFGE), ‘Ligue contre le cancer’, ‘IFR 140’, and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, Cancer Research, Chemokine, MESH : Liver Neoplasms, Hepatocellular carcinoma, MESH : Aged, MESH : Receptors, CXCR, CXCR4, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Chemokine receptor, Jurkat Cells, Mice, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH: Liver Neoplasms, MESH: Jurkat Cells, Tumor Cells, Cultured, MESH : Female, MESH: Animals, MESH: Endothelial Cells, MESH: Carcinoma, Hepatocellular, MESH : Jurkat Cells, MESH: Organ Specificity, MESH: Aged, 0303 health sciences, MESH: Middle Aged, biology, Liver cell, Liver Neoplasms, MESH: Receptors, CXCR, MESH: Gene Expression Regulation, Neoplastic, Middle Aged, 3. Good health, Gene Expression Regulation, Neoplastic, Oncology, Liver, Organ Specificity, 030220 oncology & carcinogenesis, Disease Progression, MESH: Disease Progression, Female, Liver cancer, MESH : Carcinoma, Hepatocellular, Carcinoma, Hepatocellular, MESH : Gene Expression Regulation, Neoplastic, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Mice, Inbred C57BL, MESH : Organ Specificity, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH : Mice, parasitic diseases, medicine, CXCL10, Animals, Humans, CXCL11, MESH : Middle Aged, MESH: Tumor Cells, Cultured, MESH: Mice, 030304 developmental biology, Aged, Receptors, CXCR, MESH: Humans, MESH : Endothelial Cells, MESH : Humans, Endothelial Cells, MESH : Disease Progression, medicine.disease, CXCR7, MESH: Male, Mice, Inbred C57BL, Hepatic stellate cell, biology.protein, Cancer research, MESH : Animals, MESH: Female
Abstract: International audience; Development of hepatocellular carcinoma (HCC) is a complex and progressive disease that involves cycles of liver cell death, inflammation, and tissue regeneration/remodelling. Chemokines and chemokine receptors play numerous and integral roles in the disease progression of HCC. Here we investigated the novel chemokine receptor CXCR7/RDC1 in HCC progression, its two known ligands CXCL12 and CXCL11, as well as the other CXCL12 receptor, CXCR4. Our results show that in a cohort of 408 human HCCs, CXCR7 and CXCL11 were significantly higher in tumours compared to normal liver controls (5- and 10-fold, respectively). Immunohistochemical (IHC) staining on human HCC sections confirmed that both CXCL11 and CXCR7 were much higher in cancer tissues. Furthermore, IHC staining revealed that CXCR7 protein was only expressed in endothelial cells whereas CXCL11 exhibited a much broader tissue expression. At the cellular level we observed that in vitro, human microvascular endothelial cells (HMEC-1) up-regulated CXCR7 under hypoxic and acidic pH conditions, which are well known characteristics of the HCC tumour micro-environment. As for its ligand, we observed that IFNγ robustly induced CXCL11 in hepatic stellate cells, hepatocytes, and HMEC-1s. In addition, in the mouse Diethylnitrosamine model of hepatocarcinogenesis we observed a very strong induction of CXCR7 and CXCL11 transcripts, confirming that CXCR7/CXCL11 up-regulation is conserved between human and mice liver cancer. Altogether, our results strongly support the hypothesis that the CXCL11/CXCR7 pathway is involved HCC progression.
Published: 2011

8. Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murine model of peritoneal carcinomatosis

Author: Patrick Rat, Hervé Tixier, François Radais, Delphine Delroeux, François Ghiringhelli, Sylvain Ladoire, Olivier Facy, Pablo Ortega-Deballon, Bruno Chauffert, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Chirurgie Digestive [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), This paper was supported by grants from the French National League against Cancer (Committees of Saône et Loire, Nièvre, and Côte d'Or)., BMC, Ed., Service de chirurgie digestive et cancérologie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service de chirurgie digestive [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Service d'oncologie médicale, and CHU Amiens-Picardie
Subjects: MESH : Hyperthermia, Induced, MESH : Rats, Inbred Strains, Cancer Research, Pathology, Pharmacology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Peritoneal Neoplasm, 0302 clinical medicine, MESH : Tumor Cells, Cultured, Tumor Cells, Cultured, Medicine, MESH: Peritoneal Neoplasms, MESH : Female, MESH: Animals, Peritoneal Neoplasms, Ovarian Neoplasms, MESH : Cell Survival, 0303 health sciences, MESH : Rats, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MESH: Rats, Inbred Strains, 3. Good health, MESH : Antineoplastic Agents, MESH: Ovarian Neoplasms, Epinephrine, Oncology, MESH: Cell Survival, 030220 oncology & carcinogenesis, Female, medicine.drug, Hyperthermia, medicine.medical_specialty, MESH: Rats, Cell Survival, MESH: Epinephrine, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, MESH : Cisplatin, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Peritoneal Neoplasms, In vivo, Animals, Humans, MESH: Tumor Cells, Cultured, MESH: Hyperthermia, Induced, 030304 developmental biology, Cisplatin, MESH: Humans, MESH : Ovarian Neoplasms, business.industry, Research, MESH : Humans, Rats, Inbred Strains, Hyperthermia, Induced, medicine.disease, MESH : Disease Models, Animal, Rats, Disease Models, Animal, MESH: Cisplatin, Apoptosis, MESH : Epinephrine, Cancer cell, MESH: Antineoplastic Agents, MESH : Animals, MESH: Disease Models, Animal, business, Ovarian cancer, MESH: Female
Abstract: Background The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis. Methods Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells). Results In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia. Conclusion Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.
Published: 2011

9. Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro-uracil sensitivity in human derived colon cancer cells

Author: Didier Colin, Jean-Claude Izard, Amandine Gimazane, Eric Solary, Dominique Delmas, Norbert Latruffe, Gérard Lizard, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Actichem, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), and Latruffe, Norbert
Subjects: Cancer Research, Cyclin A, Fluorescent Antibody Technique, Cell Cycle Proteins, MESH: Cell Cycle, MESH: Flow Cytometry, MESH : Blotting, Western, Resveratrol, medicine.disease_cause, Wine grape, MESH: Drug Synergism, Immunoenzyme Techniques, chemistry.chemical_compound, MESH: Phenols, MESH : Cell Cycle Proteins, MESH : Tumor Cells, Cultured, MESH: Stilbenes, Stilbenes, Tumor Cells, Cultured, MESH : Cell Proliferation, MESH: Fluorescent Antibody Technique, MESH: Antimetabolites, Antineoplastic, biology, Kinase, MESH : Antimetabolites, Antineoplastic, Cell Cycle, food and beverages, Drug Synergism, Cell cycle, Flow Cytometry, MESH : Colonic Neoplasms, Oncology, Biochemistry, Colonic Neoplasms, MESH : Fluorouracil, Fluorouracil, MESH : Phenols, Antimetabolites, Antineoplastic, MESH : Drug Synergism, MESH : Flow Cytometry, Blotting, Western, MESH : Immunoprecipitation, MESH : Stilbenes, MESH: Cell Cycle Proteins, Phenols, MESH : Immunoenzyme Techniques, MESH: Cell Proliferation, MESH : Cell Cycle, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, Immunoprecipitation, MESH: Blotting, Western, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Tumor Cells, Cultured, Kinase activity, MESH: Immunoenzyme Techniques, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Benzofurans, Cell Proliferation, MESH: Colonic Neoplasms, MESH: Humans, MESH : Benzofurans, MESH: Immunoprecipitation, MESH : Humans, MESH: Benzofurans, MESH : Fluorescent Antibody Technique, chemistry, Cell culture, biology.protein, Carcinogenesis, MESH: Fluorouracil
Abstract: International audience; Epidemiological studies suggested that trans-resveratrol, a wine grape component, could prevent malignant tumor development. This compound also demonstrated cytostatic and cytotoxic effects on tumor cells in vitro. To obtain trans-resveratrol derivatives with a better cellular uptake and enhanced antiproliferative effects, we synthesized a triacetate derivative as well as an oligomer, epsilon-viniferin and its acetylated form, epsilon-viniferin penta-acetate. We also obtained vineatrol, a wine grape shoot extract that associates several polyphenols that may act synergistically, including trans-resveratrol and epsilon-viniferin. We show here that resveratrol triacetate and vineatrol are as efficient as trans-resveratrol in inducing the accumulation of human colon cancer cells in early S phase of the cell cycle. This effect is associated with a nuclear redistribution of cyclin A and the formation of a cyclin A/cyclin-dependent kinase 2 complex whose kinase activity is increased. In contrast, epsilon-viniferin and its acetylated form do not demonstrate any significant activity on these cells when tested alone. Interestingly, resveratrol triacetate and vineatrol dramatically enhance 5-Fluoro-Uracil-mediated inhibition of colon cancer cell proliferation. Thus, acetylated derivatives of resveratrol have retained the cytostatic and cytotoxic activities of the parental molecule and thus deserve to be tested as chemosensitizers in animal models.
Published: 2009

10. Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes

Author: Fabienne Meggetto, Alan Bénard, Nadine Cogne, Aurélie Chanut, Nathalie Faumont, Georges Delsol, Jean Feuillard, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Centre de Physiopathologie Toulouse Purpan, and Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH : Cell Line, MESH : Molecular Sequence Data, DNA Mutational Analysis, MESH: NF-kappa B, Apoptosis, MESH: Base Sequence, medicine.disease_cause, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH: Luciferases, Renilla, immune system diseases, hemic and lymphatic diseases, MESH : Hodgkin Disease, Tumor Cells, Cultured, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Viral Matrix Proteins, MESH: Genetic Variation, Reed-Sternberg Cells, MESH: DNA Mutational Analysis, MESH : Immunoblotting, MESH: Reed-Sternberg Cells, Oncogene Proteins, Genetics, B-Lymphocytes, 0303 health sciences, Mutation, MESH: Immunoblotting, MESH : Oncogene Proteins, NF-kappa B, Hematology, Transfection, Hodgkin Disease, MESH: Hodgkin Disease, MESH : NF-kappa B, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Mutation, MESH : Transfection, MESH: Mutation, MESH : Recombinant Fusion Proteins, Recombinant Fusion Proteins, Immunoblotting, Molecular Sequence Data, MESH : Luciferases, Renilla, MESH : DNA Mutational Analysis, Biology, MESH: Sequence Homology, Nucleic Acid, MESH : B-Lymphocytes, Cell Line, Viral Matrix Proteins, 03 medical and health sciences, MESH: Oncogene Proteins, stomatognathic system, MESH : Genetic Variation, Sequence Homology, Nucleic Acid, MESH: B-Lymphocytes, medicine, otorhinolaryngologic diseases, MESH: Recombinant Fusion Proteins, Animals, Humans, Hodgkin's Lymphoma, MESH : Sequence Homology, Nucleic Acid, MESH: Tumor Cells, Cultured, Luciferases, Renilla, 030304 developmental biology, MESH: Viral Matrix Proteins, MESH: Molecular Sequence Data, MESH: Humans, MESH : Reed-Sternberg Cells, Base Sequence, MESH: Apoptosis, MESH: Transfection, MESH : Humans, Genetic Variation, medicine.disease, Hodgkin's lymphoma, Epstein–Barr virus, Lymphoma, MESH: Cell Line, stomatognathic diseases, Reed–Sternberg cell, Cell culture, Cancer research, MESH : Base Sequence, MESH : Animals, Carcinogenesis, MESH : Apoptosis
Abstract: International audience; BACKGROUND: In Epstein-Barr virus-associated Hodgkin's lymphomas, neoplastic Reed-Sternberg cells and surrounding non-tumor B-cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-cells. DESIGN AND METHODS: Twelve LMP1 natural variants from Reed-Sternberg cells, non-tumor B-cells of Hodgkin's lymphomas and from B-cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 cells to search for relationships between LMP1 cellular origin and oncogenic properties as well as nuclear factor-kappaB activation, and apoptosis protection. RESULTS: LMP1 variants of Reed-Sternberg cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg cells, but inconstantly for LMP1-variants from non-tumor B-cells. Analysis of LMP1 variants from both normal B-cells and Reed-Sternberg cells indicates that protection against apoptosis through activation of nuclear factor-kappaB - whatever the cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. CONCLUSIONS: Taken together, our results demonstrate that preserved nuclear factor-kappaB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor cells in Hodgkin's lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg cells.
Published: 2009

11. Placental and fetal steroidogenesis

Author: Sanderson , J Thomas, Institut Armand Frappier ( INRS-IAF ), and Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier
Subjects: MESH : Pregnancy, MESH : RNA, Messenger, MESH : Tumor Cells, Cultured, MESH : Placenta, MESH : Humans, [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, MESH : Aromatase, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH : Base Sequence, MESH : DNA Primers, MESH : Female, MESH : Fetus, MESH : Steroids
Abstract: International audience; Steroid hormones are essential for maintenance of pregnancy and fetal development. The expression and catalytic activity of the key steroidogenic enzymes involved in the production of progesterone and estrogens increase during pregnancy, and there is an intricate communication between the mother, the placenta, and the fetus in order to maintain a balanced supply of the steroid hormones essential for embryogenesis. This chapter describes methods for the measurement of the expression and catalytic activity of three key cytochrome P450 (CYP) enzymes involved in the production of progesterone and estrogens, aromatase (CYP19), steroid 17-hydroxylase/17,20-lyase (CYP17), and cholesterol side-chain cleavage (CYP11A).
Published: 2009

12. Autophagy: a novel mechanism of synergistic cytotoxicity between doxorubicin and roscovitine in a sarcoma model

Author: Laurent Meijer, Gordon B. Mills, Khandan Keyomarsi, Donald H. Lambert, Laura A. Lambert, Na Qiao, Kelly K. Hunt, Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Program in integrative biology. Research Institute, The Hospital for sick children [Toronto] (SickKids), Unité de Chimie Pharmaceutique et Radiopharmacie (UCL-CMFA 7340), Université Catholique de Louvain = Catholic University of Louvain (UCL), School of Environmental Sciences [Norwich], University of East Anglia [Norwich] (UEA), Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Biogéosciences [Dijon] ( BGS ), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), The Hospital for Sick Children, Unité de Chimie Pharmaceutique et Radiopharmacie ( UCL-CMFA 7340 ), Université Catholique de Louvain ( UCL ), University of East Anglia [Norwich] ( UEA ), Molécules et cibles thérapeutiques ( MCT ), and Centre National de la Recherche Scientifique ( CNRS )
Subjects: Cancer Research, Cell cycle checkpoint, MESH : Antineoplastic Combined Chemotherapy Protocols, medicine.medical_treatment, Apoptosis, MESH : Models, Biological, Pharmacology, MESH: Drug Synergism, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH : Cytotoxins, Antineoplastic Combined Chemotherapy Protocols, Tumor Cells, Cultured, MESH : G2 Phase, MESH : Purines, Cytotoxicity, Tumor Stem Cell Assay, 0303 health sciences, Cytotoxins, MESH: Tumor Stem Cell Assay, Drug Synergism, Sarcoma, MESH: Purines, Cell cycle, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, 030220 oncology & carcinogenesis, MESH: Cytotoxins, medicine.drug, G2 Phase, MESH : Drug Synergism, MESH : Tumor Stem Cell Assay, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH : Sarcoma, Models, Biological, Article, 03 medical and health sciences, MESH: Doxorubicin, Therapeutic index, medicine, Autophagy, Roscovitine, MESH : Doxorubicin, MESH: Autophagy, Humans, Doxorubicin, MESH: Tumor Cells, Cultured, 030304 developmental biology, Chemotherapy, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Apoptosis, MESH : Humans, MESH: Models, Biological, MESH : Autophagy, MESH: G2 Phase, Purines, MESH: Sarcoma, MESH : Apoptosis
Abstract: Doxorubicin is a genotoxic chemotherapy agent used in treatment of a wide variety of cancers. Significant clinical side effects, including cardiac toxicity and myelosuppression, severely limit the therapeutic index of this commonly used agent and methods which improve doxorubicin efficacy could benefit many patients. Because doxorubicin cytotoxicity is cell cycle specific, the cell cycle is a rational target to enhance its efficacy. We examined the direct, cyclin-dependent kinase inhibitor roscovitine as a means of enhancing doxorubicin cytotoxicity. This study showed synergistic cytotoxicity between doxorubicin and roscovitine in three sarcoma cell lines: SW-982 (synovial sarcoma), U2OS-LC3-GFP (osteosarcoma), and SK-LMS-1 (uterine leiomyosarcoma), but not the fibroblast cell line WI38. The combined treatment of doxorubicin and roscovitine was associated with a prolonged G2-M cell cycle arrest in the three sarcoma cell lines. Using three different methods for detecting apoptosis, our results revealed that apoptotic cell death did not account for the synergistic cytotoxicity between doxorubicin and roscovitine. However, morphologic changes observed by light microscopy and increased cytoplasmic LC3-GFP puncta in U20S-LC3-GFP cells after the combined treatment suggested the induction of autophagy. Induction of autophagy was also shown in SW-982 and SK-LMS-1 cells treated with both doxorubicin and roscovitine by acridine orange staining. These results suggest a novel role of autophagy in the enhanced cytotoxicity by cell cycle inhibition after genotoxic injury in tumor cells. Further investigation of this enhanced cytotoxicity as a treatment strategy for sarcomas is warranted. [Cancer Res 2008;68(19):7966–74]
Published: 2008

13. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. : hepatocellular tumors miRNA profiling

Author: Ladeiro , Yannick, Couchy , Gabrielle, Balabaud , Charles, Bioulac-Sage , Paulette, Pelletier , Laura, Rebouissou , Sandra, Zucman-Rossi , Jessica, Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, and This work was supported by the ANRS, Inserm (Réseaux de recherche clinique et réseaux de recherche en santé des populations), and the program 'Carte d'identité des tumeurs' initiated, developed and funded by the Ligue Nationale Contre le Cancer. YL is supported by an ANRS doctoral fellowship. JZR is supported by a 'contrat d'interface' between Inserm and CHU Bordeaux.
Subjects: MESH : Carcinoma, Hepatocellular, MESH : Liver Neoplasms, Hepatocellular carcinoma, MESH : Gene Expression Regulation, Neoplastic, MESH : Genes, Tumor Suppressor, ß-catenin, Benign and malignant tumors, liver cell adenoma, MESH : Tumor Cells, Cultured, Focal nodular hyperplasia, HBV, Alcohol consumption, miRNA, MESH : Gene Expression Profiling, MESH : Humans, biomarkers, MESH : beta Catenin, Hepatocellular adenoma, MESH : Risk Factors, HNF1a, MESH : MicroRNAs, MESH : Phenotype, HCV, MESH : Hepatocyte Nuclear Factor 1-alpha, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH : Mutation, microarray, transcriptome
Abstract: International audience; Molecular classifications defining new tumor subtypes have been recently refined with genetic and transcriptomic analyses of benign and malignant hepatocellular tumors. Here, we performed microRNA (miRNA) profiling in two series of fully annotated liver tumors to uncover associations between oncogene/tumor suppressor mutations and clinical and pathological features. Expression levels of 250 miRNAs in 46 benign and malignant hepatocellular tumors were compared to those of 4 normal liver samples with quantitative reverse-transcriptase polymerase chain reaction. miRNAs associated with genetic and clinical characteristics were validated in a second series of 43 liver tumor samples and 16 nontumor samples. miRNA profiling unsupervised analysis classified samples in unique clusters characterized by histological features (tumor/nontumor, P < 0.001; benign/malignant tumors, P < 0.01; inflammatory adenoma and focal nodular hyperplasia, P < 0.01), clinical characteristics [hepatitis B virus (HBV) infection, P < 0.001; alcohol consumption, P < 0.05], and oncogene/tumor suppressor gene mutations [beta-catenin, P < 0.01; hepatocyte nuclear factor 1alpha (HNF1alpha), P < 0.01]. Our study identified and validated miR-224 overexpression in all tumors and miR-200c, miR-200, miR-21, miR-224, miR-10b, and miR-222 specific deregulation in benign or malignant tumors. Moreover, miR-96 was overexpressed in HBV tumors, and miR-126* was down-regulated in alcohol-related hepatocellular carcinoma. Down-regulations of miR-107 and miR-375 were specifically associated with HNF1alpha and beta-catenin gene mutations, respectively. miR-375 expression was highly correlated to that of beta-catenin-targeted genes as miR-107 expression was correlated to that of HNF1alpha in a small interfering RNA cell line model. Thus, this strongly suggests that beta-catenin and HNF1alpha could regulate miR-375 and miR-107 expression levels, respectively. CONCLUSION: Hepatocellular tumors may have a distinct miRNA expression fingerprint according to malignancy, risk factors, and oncogene/tumor suppressor gene alterations. Dissecting these relationships provides a new hypothesis to understand the functional impact of miRNA deregulation in liver tumorigenesis and the promising use of miRNAs as diagnostic markers.
Published: 2008

14. PAI-1 and functional blockade of SNAI1 in breast cancer cell migration

Author: José Palacios, Amparo Cano, Amandine Cartier-Michaud, Gema Moreno-Bueno, Elizabeth Fabre-Guillevin, Benoît Vallée, Michel Malo, Georgia Barlovatz-Meimon, Daniel A. Lawrence, Héctor Peinado, Cécile Charrière-Bertrand, Hôpital Européen Georges Pompidou [APHP] (HEGP), DYNAMIC, Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS) - Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS), Centre National d'Investigations Oncologiques (CNIO), CNIO, Laboratoire de recherche sur la croissance cellulaire, la réparation et la régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Centre National de la Recherche Scientifique (CNRS), Servicio de Anatomia Patologica, Hospital Virgen del Rocío, Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS) - Université d'Évry-Val-d'Essonne (UEVE) - Centre National de la Recherche Scientifique (CNRS) - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Spanish National Cancer Research Center (CNIO), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario Virgen del Rocío [Sevilla], and Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)
Subjects: MESH : RNA, Messenger, MESH : Transcription Factors, MESH : Wound Healing, Fluorescent Antibody Technique, Snail, MESH : Breast Neoplasms, MESH: Cadherins, MESH: Plasminogen Activator Inhibitor 1, Metastasis, Immunoenzyme Techniques, chemistry.chemical_compound, 0302 clinical medicine, MESH : Tumor Cells, Cultured, Cell Movement, MESH: Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, MESH : Cell Movement, MESH : Female, Pseudopodia, Receptor, MESH: Cell Movement, MESH: Fluorescent Antibody Technique, Genes, Dominant, Oligonucleotide Array Sequence Analysis, Medicine(all), 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, MESH : Reverse Transcriptase Polymerase Chain Reaction, Cell migration, MESH : Urokinase-Type Plasminogen Activator, MESH: Transcription Factors, MESH : Genes, Dominant, Cadherins, 3. Good health, MESH : Oligonucleotide Array Sequence Analysis, 030220 oncology & carcinogenesis, Plasminogen activator inhibitor-1, Female, MESH : Cadherins, Research Article, MESH : Plasminogen Activator Inhibitor 1, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Urokinase-Type Plasminogen Activator, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH : Immunoenzyme Techniques, biology.animal, Plasminogen Activator Inhibitor 1, medicine, Humans, RNA, Messenger, MESH: Tumor Cells, Cultured, MESH: Immunoenzyme Techniques, Cell adhesion, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: RNA, Messenger, 030304 developmental biology, Wound Healing, MESH: Humans, Gene Expression Profiling, MESH : Gene Expression Profiling, MESH : Humans, Cancer, medicine.disease, Urokinase-Type Plasminogen Activator, Molecular biology, MESH: Wound Healing, MESH : Fluorescent Antibody Technique, chemistry, MESH: Pseudopodia, MESH: Oligonucleotide Array Sequence Analysis, SNAI1, MESH : Pseudopodia, Cancer research, Snail Family Transcription Factors, MESH: Genes, Dominant, MESH: Female, MESH: Breast Neoplasms, Transcription Factors
Abstract: International audience; INTRODUCTION: Snail, a family of transcriptional repressors implicated in cell movement, has been correlated with tumour invasion. The Plasminogen Activation (PA) system, including urokinase plasminogen activator (uPA), its receptor and its inhibitor, plasminogen activator inhibitor type 1(PAI-1), also plays a key role in cancer invasion and metastasis, either through proteolytic degradation or by non-proteolytic modulation of cell adhesion and migration. Thus, Snail and the PA system are both over-expressed in cancer and influence this process. In this study we aimed to determine if the activity of SNAI1 (a member of the Snail family) is correlated with expression of the PA system components and how this correlation can influence tumoural cell migration. METHODS: We compared the invasive breast cancer cell-line MDA-MB-231 expressing SNAI1 (MDA-mock) with its derived clone expressing a dominant-negative form of SNAI1 (SNAI1-DN). Expression of PA system mRNAs was analysed by cDNA microarrays and real-time quantitative RT-PCR. Wound healing assays were used to determine cell migration. PAI-1 distribution was assessed by immunostaining. RESULTS: We demonstrated by both cDNA microarrays and real-time quantitative RT-PCR that the functional blockade of SNAI1 induces a significant decrease of PAI-1 and uPA transcripts. After performing an in vitro wound-healing assay, we observed that SNAI1-DN cells migrate more slowly than MDA-mock cells and in a more collective manner. The blockade of SNAI1 activity resulted in the redistribution of PAI-1 in SNAI1-DN cells decorating large lamellipodia, which are commonly found structures in these cells. CONCLUSIONS: In the absence of functional SNAI1, the expression of PAI-1 transcripts is decreased, although the protein is redistributed at the leading edge of migrating cells in a manner comparable with that seen in normal epithelial cells.
Published: 2008

15. Synthesis, structure, and estrogenic activity of 4-amino-3-(2-methylbenzyl)coumarins on human breast carcinoma cells

Author: Yves Jacquot, Denis Nonclercq, Guy Laurent, Anny Cleeren, Alain Xicluna, Laurent Bermont, Kamal Boubekeur, Ioanna Laïos, Guy Leclercq, Bernard Refouvelet, Synthèse, Structure et Fonction de Molécules Bioactives (SSFMB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Histology, Faculty of Medicine and Pharmacy, Université de Mons-Hainaut, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Chimie Inorganique et Matériaux Moléculaires (CIM2), Laboratoire de catalyse de Lille - UMR 8010 (LCL), Université de Lille, Sciences et Technologies-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Synthèse, Structure et Fonction de Molécules Bioactives ( SSFMB ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Mons-Hainaut (UMH), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire de Chimie Inorganique et Matériaux Moléculaires ( CIM2 ), Laboratoire de catalyse de Lille ( LCL ), and Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Ecole Nationale Supérieure de Chimie de Lille ( ENSCL ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Models, Molecular, Transcription, Genetic, Clinical Biochemistry, Pharmaceutical Science, Estrogen receptor, MESH : Breast Neoplasms, MESH : Promoter Regions, Genetic, Ligands, 01 natural sciences, Biochemistry, MESH: Estrogens, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Transactivation, MESH : Tumor Cells, Cultured, Coumarins, Drug Discovery, Tumor Cells, Cultured, MESH : Cell Proliferation, MESH: Ligands, MESH : Transcriptional Activation, Luciferases, Promoter Regions, Genetic, MESH : Ligands, 0303 health sciences, Molecular Structure, Chemistry, Biological activity, Transfection, MESH: Coumarins, MESH : Thymidine Kinase, 3. Good health, Cell biology, MESH : Antineoplastic Agents, Receptors, Estrogen, Molecular Medicine, MESH: Receptors, Estrogen, MESH: Models, Molecular, medicine.drug, Transcriptional Activation, MESH: Thymidine Kinase, medicine.medical_specialty, MESH : Models, Molecular, MESH: Molecular Structure, Antineoplastic Agents, Breast Neoplasms, MESH : Coumarins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Thymidine Kinase, 03 medical and health sciences, Internal medicine, MESH: Cell Proliferation, MESH: Promoter Regions, Genetic, medicine, Humans, MESH: Tumor Cells, Cultured, Molecular Biology, Cell Proliferation, 030304 developmental biology, MESH : Luciferases, MESH: Humans, Fulvestrant, 010405 organic chemistry, Cell growth, MESH: Transcription, Genetic, MESH : Humans, Organic Chemistry, MESH : Transcription, Genetic, Estrogens, Antiestrogen, 0104 chemical sciences, Endocrinology, Cell culture, MESH : Receptors, Estrogen, MESH: Antineoplastic Agents, MESH: Transcriptional Activation, MESH : Estrogens, MESH: Luciferases, MESH : Molecular Structure, MESH: Breast Neoplasms
Abstract: International audience; A number of coumarins exhibit interesting pharmacological activities and are therefore of therapeutic use. We report here the synthesis and the structural analysis of new N-substituted 4-amino-3-(2-methylbenzyl)coumarins (compounds 8a-8e) that present structural analogies with estrothiazine and 11- or 7-substituted 17beta-estradiol. These derivatives were tested with respect to estrogenic activity on the estrogen receptor positive (ER+) human MCF-7 breast cancer cell line. Two of the reported compounds (8a and 8b) stimulated specifically the proliferation of MCF-7 cells, but not that of estrogen receptor negative (ER-) human MDA-MB-231 breast cancer cells, suggesting that their mitogenic activity is mediated by ER. Accordingly, the stimulating effect of 8a and 8b was suppressed by the pure antiestrogen fulvestrant. Besides, 8a and 8b induced ER down-regulation similar to that produced by classical ER agonists or pure antagonists. The effects of the compounds under study on ER-mediated transcription were assessed on (ER+) MVLN cells, that is, MCF-7 cells stably transfected with a pVit-tk-Luc reporter plasmid. Derivatives 8a and 8b, and surprisingly compound 8c, enhanced ER-mediated gene transactivation in that model. Finally, no coumarin was able to compete with tritiated 17beta-estradiol ([(3)H]E(2)) for ER binding, suggesting unconventional interactions with the receptor, such as interactions with the second binding pocket or with the coactivator-binding region. To conclude, observations performed in this study on compound 8c reveal that estrogenic activity can be dissociated from enhancement of cell proliferation. Furthermore, ERE-driven transactivation of transcription seems to be a condition necessary, but not sufficient, for estrogen-induced stimulation of cell growth.
Published: 2007

16. Rapamycin inhibits growth and survival of D-816-V-mutated c-kit mast cells

Author: Yves Lepelletier, Olivier Lortholary, Guy Laurent, Martine Humbert, Olivier Hermine, Jean Pierre Zappulla, Antoine Ribadeau-Dumas, Marion Gabillot-Carré, Nadine Ben Hamouda, Paulo de Sepuvelda, Christian Recher, Emmanuel Morelon, Christine Bodemer, François Machavoine, Cédric Baude, Aurélie Hermant, Patrice Dubreuil, Jacques Vargaftig, Michel Arock, Sébastien Letard, Michel Dy, Roland S. Liblau, Ying Yang, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'immunologie, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Cancérologie, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cancérologie (Inserm U599/IPC), Université de la Méditerranée - Aix-Marseille 2-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département Immunologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Slama, Catherine, Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Signal Transduction, MESH : Brain Mapping, Apoptosis, medicine.disease_cause, Biochemistry, MESH: Magnetic Resonance Imaging, MESH : Auditory Perception, Mice, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH : Neural Pathways, MESH : Cell Proliferation, Tumor Cells, Cultured, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, Mast Cells, Systemic mastocytosis, MESH: Mastocytosis, Systemic, MESH: Brain Mapping, MESH : Cell Survival, 0303 health sciences, Mutation, MESH: Music, TOR Serine-Threonine Kinases, MESH : Music, MESH : Mastocytosis, Systemic, MESH: Mast Cells, Hematology, MESH : Mice, Transgenic, MESH: Positron-Emission Tomography, 3. Good health, MESH: Proto-Oncogene Proteins c-kit, Proto-Oncogene Proteins c-kit, MESH: Cell Survival, Phosphorylation, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Mast Cells, MESH : Pharmacogenetics, Tyrosine kinase, MESH : Time Factors, medicine.drug, Signal Transduction, Cell Survival, MESH: Mice, Transgenic, Immunology, Mutation, Missense, MESH: Acoustic Stimulation, MESH: Pharmacogenetics, Mice, Transgenic, MESH : Protein Kinases, Biology, MESH : Proto-Oncogene Proteins c-kit, MESH : Emotions, 03 medical and health sciences, MESH: Auditory Perception, MESH: Brain, Mastocytosis, Systemic, MESH: Models, Neurological, MESH : Magnetic Resonance Imaging, MESH: Cell Proliferation, MESH : Mice, medicine, MESH : Models, Neurological, Animals, Humans, MESH: Tumor Cells, Cultured, MESH: Mice, MESH: Protein Kinases, PI3K/AKT/mTOR pathway, 030304 developmental biology, Cell Proliferation, MESH: Emotions, MESH : Signal Transduction, Sirolimus, MESH: Mutation, Missense, MESH: Humans, MESH : Sirolimus, MESH: Apoptosis, MESH: Neural Pathways, MESH : Humans, RPTOR, MESH: Time Factors, MESH : Positron-Emission Tomography, Cell Biology, MESH : Acoustic Stimulation, medicine.disease, MESH : Brain, Pharmacogenetics, Cancer research, MESH : Animals, MESH: Sirolimus, Protein Kinases, MESH : Apoptosis, MESH : Mutation, Missense, 030215 immunology
Abstract: International audience; Two classes of oncogenic mutations of the c-kit tyrosine kinase have been described: the juxtamembrane domain V560G mutation, which is preferentially found in gastrointestinal stromal tumors (GISTs), and the kinase domain D816V mutation, which is highly representative of systemic mastocytosis (SM). Here we show that both mutations constitutively activate the mammalian target of rapamycin (mTOR) signaling pathway. Surprisingly, the mTOR inhibitor rapamycin induces only apoptosis in HMC-1 cells bearing the D816V but not the V560G mutation. In support of this unexpected selectivity, rapamycin inhibits the phosphorylation of 4E-BP1, a downstream substrate of the mTOR pathway, but only in D816V HMC-1 cells. Importantly, D816V mast cells isolated from SM patients or from transgenic mice are sensitive to rapamycin whereas normal human or mouse mast cells are not. Thus, rapamycin inhibition appears specific to the D816V mutation. At present there is no effective cure for SM patients with the D816V mutation. The data presented here provide a rationale to test whether rapamycin could be a possible treatment for SM and other hematologic malignancies with the D816V mutation.
Published: 2006

17. Morphine cross-reacts with somatostatin receptor SSTR2 in the T47D human breast cancer cell line and decreases cell growth

Author: Hatzoglou, A., L’Houcine Ouafik, Bakogeorgou, E., Thermos, K., Castanas, E., Medical School, University of Crete, Heraklion, Greece, Medical School, University of Crete, INSERM U 297 - Laboratoire de Neuroendocrinologie Expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Ouafik, L'Houcine
Subjects: Narcotics, MESH : Molecular Sequence Data, MESH : RNA, Messenger, MESH : Narcotics, MESH: Somatostatin, Molecular Sequence Data, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Breast Neoplasms, MESH: Base Sequence, Octreotide, MESH : Octreotide, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Hormone Antagonists, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Tumor Cells, Cultured, Tumor Cells, Cultured, MESH: Receptors, Somatostatin, Humans, MESH : Female, RNA, Messenger, Receptors, Somatostatin, MESH : Endorphins, MESH: Tumor Cells, Cultured, MESH: RNA, Messenger, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Morphine, MESH : Somatostatin, MESH: Octreotide, MESH: Endorphins, MESH : Humans, MESH : Morphine, MESH : Cell Division, MESH : Receptors, Somatostatin, MESH: Narcotics, MESH: Morphine, MESH: Hormone Antagonists, MESH: Cell Division, Female, MESH : Base Sequence, Endorphins, Somatostatin, MESH: Female, Cell Division, MESH: Breast Neoplasms, MESH : Hormone Antagonists
Abstract: International audience; In a previous study, we found that morphine decreases, in a dose-dependent manner, the cell growth of T47D human breast cancer cells, despite the lack of mu opioid receptors and an interaction of morphine with other opioid sites. We have therefore examined a possible interaction of morphine with other membrane receptor systems of the cell. The present study describes for the first time an interaction between mu-acting opioid drugs and the somatostatinergic system. We have found that [125I]Tyr11-somatostatin binds with high affinity to T47D cells. Analysis of the binding data showed the presence of two components: one with high affinity but low capacity (Kd, 0.145 nM; 1450 sites/cell), and another of lower affinity but higher capacity (Kd, 1.192 nM; 11920 sites/cell). Somatostatin-14 and somatostatin-28 showed multiphasic displacement curves, indicating heterogeneity of binding sites. The latter was confirmed by reverse transcription-PCR, which revealed the existence of the somatostatin receptor subtypes 2 and 3 (SSTR2 and SSTR3), with a relative mRNA concentration of 85 and 15%, respectively. Morphine and the morphinomimetic peptide morphiceptine (Tyr-Pro-Phe-Pro-NH2) displace somatostatin from its binding sites. Further analysis indicated that mu-acting opioids interact with the SSTR2 receptor subtype.
Published: 1995

18. Human melanoma cell lines differ in their capacity to release ADP and aggregate platelets

Author: Boukerche , H., Berthier-Vergnes , O., Penin , F., Tabone , E., Lizard , G., Bailly , M., McGregor , J. L., Laviron, Nathalie, Fonctions Normales et Pathologiques de la Barrière Cutanée [Hôpital Edouard Herriot - HCL], Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Peau humaine et immunité, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de génétique et de physiologie moléculaire et cellulaire ( CGPhiMC ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Laboratoire des Lipoprotéines humaines et interactions vasculaires, Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire de Biochimie Moléculaire et Cellulaire ( LBMC ), Université de Bourgogne ( UB ), Centre Léon Bérard [Lyon], and Deleage, Gilbert
Subjects: MESH : Chromatography, High Pressure Liquid, MESH : Platelet Aggregation, MESH : Tumor Cells, Cultured, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Humans, MESH : Receptors, Cytoadhesin, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Melanoma, MESH : Adenosine Diphosphate, MESH : Integrins, MESH : Receptors, Vitronectin, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH : Microscopy, Electron
Abstract: In this study we have investigated, using three different human melanoma cell lines (M1Do., M3Da., M4Be.). the varying capacity of melanoma cells to induce platelet aggregation in the presence or absence of inhibitors of ADP or thrombin. The expression levels of different integrins (alpha v, beta 3, alpha v beta 3, alpha IIb, alpha v beta 3) were evaluated by immunoprecipitation, binding and flow cytometry studies. The level of ADP in supernatants of melanoma cells were quantified by ADP bioassay and HPLC. Platelets were irreversibly aggregated by M3Da, as shown by electron microscopy, in contrast to M1Do, which induced a slow reversible aggregation. M4Be. did not induce platelet aggregation. In both cases, with M3Da. or M1Do., apyrase but not PPACK inhibited platelet induced aggregation. An anti-alpha v beta 3 monoclonal antibody (LYP18) or polyclonal antibody inhibited platelet aggregation. A similar number of LYP18 molecules bound to the surface of M1Do., M3Da. and M4Be. cell lines. Biological HPLC assays of ADP present in the supernatant of tumour cell lines showed the highest concentration of ADP to be secreted by M3Da., followed by M1Do., and none detected for M4Be. These results show that differences in in vitro aggregating potential of the three human melanoma cell lines are not related to low integrin expression levels but to their ability to generate ADP. Generation of ADP by human melanoma cells may act as important modulator of melanoma-platelet interactions.In this study we have investigated, using three different human melanoma cell lines (M1Do., M3Da., M4Be.). the varying capacity of melanoma cells to induce platelet aggregation in the presence or absence of inhibitors of ADP or thrombin. The expression levels of different integrins (alpha v, beta 3, alpha v beta 3, alpha IIb, alpha v beta 3) were evaluated by immunoprecipitation, binding and flow cytometry studies. The level of ADP in supernatants of melanoma cells were quantified by ADP bioassay and HPLC. Platelets were irreversibly aggregated by M3Da, as shown by electron microscopy, in contrast to M1Do, which induced a slow reversible aggregation. M4Be. did not induce platelet aggregation. In both cases, with M3Da. or M1Do., apyrase but not PPACK inhibited platelet induced aggregation. An anti-alpha v beta 3 monoclonal antibody (LYP18) or polyclonal antibody inhibited platelet aggregation. A similar number of LYP18 molecules bound to the surface of M1Do., M3Da. and M4Be. cell lines. Biological HPLC assays of ADP present in the supernatant of tumour cell lines showed the highest concentration of ADP to be secreted by M3Da., followed by M1Do., and none detected for M4Be. These results show that differences in in vitro aggregating potential of the three human melanoma cell lines are not related to low integrin expression levels but to their ability to generate ADP. Generation of ADP by human melanoma cells may act as important modulator of melanoma-platelet interactions.
Published: 1994

19. Preferential coupling between dopamine D2 receptors and G-proteins

Author: Jean-Pierre Montmayeur, Janique Guiramand, Emiliana Borrelli, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie de l'audition-plasticité synaptique, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] ( IBMM ), and Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH: Signal Transduction, MESH : RNA, Messenger, Dopamine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Messenger, MESH : Adenylate Cyclase, Receptors, Dopamine, Adenylyl cyclase, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, MESH : 1-Methyl-3-isobutylxanthine, MESH : Tumor Cells, Cultured, 1-Methyl-3-isobutylxanthine, Receptors, Tumor Cells, Cultured, MESH : Receptors, Dopamine, MESH: Receptors, Dopamine, Receptor, MESH : GTP-Binding Proteins, 0303 health sciences, Cultured, ADCY9, MESH: 1-Methyl-3-isobutylxanthine, General Medicine, Tumor Cells, MESH : Forskolin, MESH : Spiperone, Biochemistry, Dopamine receptor, Spiperone, MESH: Spiperone, MESH : RNA Splicing, Signal transduction, MESH : Transfection, MESH: Forskolin, Forskolin, Signal Transduction, Adenylate Cyclase, MESH: GTP-Binding Proteins, MESH : Dopamine, G protein, RNA Splicing, MESH: Dopamine, Biology, Transfection, ADCY10, 03 medical and health sciences, GTP-Binding Proteins, Dopamine receptor D2, MESH: Adenylate Cyclase, Humans, RNA, Messenger, MESH: Tumor Cells, Cultured, Molecular Biology, 030304 developmental biology, MESH: RNA, Messenger, MESH : Signal Transduction, MESH: Humans, MESH: Transfection, Colforsin, MESH : Humans, chemistry, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adenylyl Cyclase Inhibitors, RNA, MESH: RNA Splicing, 030217 neurology & neurosurgery
Abstract: International audience; The D2 dopamine receptor, an inhibitor of adenylyl cyclase, belongs to the family of seven transmembrane domain G-protein-coupled receptors. This receptor is encoded by two mRNAs produced from the same gene by alternative splicing, here referred to as D2L and D2S. The resultant proteins are identical except for an insertion of 29 amino acids in the putative third intracytoplasmic domain. This domain has been shown to be important for the coupling of this family of receptors to G-proteins. We have previously shown that there is differential inhibition of the adenylyl cyclase activity when these two receptors are produced in JEG3 cells; D2S is more efficient than D2L. To understand the molecular basis of such differential activity, we analyzed the G-proteins expressed in these cells. Here we show that G alpha i2 is absent in this cell line. Moreover, it is possible to restore the same inhibitory activity obtained by D2S when an expression vector encoding this alpha-subunit is cotransfected with D2L. In addition, transfections of the two receptors in a recipient cell line containing the three G alpha i subtypes confirm that the two receptors behave similarly. We conclude that the 29-amino acid insertion present in D2L allows it to interact specifically with G alpha i2. These data suggest that in vivo the function of activated D2 receptors is exerted by specific interactions with Gi-protein subtypes.
Published: 1993

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19 results on '"MESH : Tumor Cells, Cultured"'

1. Sex differences in the GSK3β-mediated survival of adherent leukemic progenitors

2. miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers

3. Selective mRNA degradation by antisense oligonucleotide-2,5A chimeras: Involvement of RNase H and RNase L

4. A protocol to quantify mammary early common progenitors from long-term mammosphere culture

5. Autocrine proliferative effects of hGH are maintained in primary cultures of human mammary carcinoma cells

6. Accumulation of lactosylceramide and overexpression of a PSC833-resistant P-glycoprotein in multidrug-resistant human sarcoma cells

7. CXCR7 is up-regulated in human and murine hepatocellular carcinoma and is specifically expressed by endothelial cells

8. Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murine model of peritoneal carcinomatosis

9. Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro-uracil sensitivity in human derived colon cancer cells

10. Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes

11. Placental and fetal steroidogenesis

12. Autophagy: a novel mechanism of synergistic cytotoxicity between doxorubicin and roscovitine in a sarcoma model

13. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. : hepatocellular tumors miRNA profiling

14. PAI-1 and functional blockade of SNAI1 in breast cancer cell migration

15. Synthesis, structure, and estrogenic activity of 4-amino-3-(2-methylbenzyl)coumarins on human breast carcinoma cells

16. Rapamycin inhibits growth and survival of D-816-V-mutated c-kit mast cells

17. Morphine cross-reacts with somatostatin receptor SSTR2 in the T47D human breast cancer cell line and decreases cell growth

18. Human melanoma cell lines differ in their capacity to release ADP and aggregate platelets

19. Preferential coupling between dopamine D2 receptors and G-proteins

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19 results on '"MESH : Tumor Cells, Cultured"'

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