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103 results on '"Dumond, Hélène"'

1. A statistical methodology to select covariates in high-dimensional data under dependence. Application to the classification of genetic profiles in oncology

Author

Bastien, Bérangère, Boukhobza, Taha, Dumond, Hélène, Gégout-Petit, Anne, Muller-Gueudin, Aurélie, and Thiébaut, Charlène

Subjects
Mathematics - Statistics Theory, Statistics - Applications, Statistics - Methodology
Abstract

We propose a new methodology for selecting and ranking covariates associated with a variable of interest in a context of high-dimensional data under dependence but few observations. The methodology successively intertwines the clustering of covariates, decorrelation of covariates using Factor Latent Analysis, selection using aggregation of adapted methods and finally ranking. Simulations study shows the interest of the decorrelation inside the different clusters of covariates. We first apply our method to transcriptomic data of 37 patients with advanced non-small-cell lung cancer who have received chemotherapy, to select the transcriptomic covariates that explain the survival outcome of the treatment. Secondly, we apply our method to 79 breast tumor samples to define patient profiles for a new metastatic biomarker and associated gene network in order to personalize the treatments.

Published
2019

5. GPER agonist G-1 disrupts tubulin dynamics and potentiates temozolomide to impair glioblastoma cell proliferation

Author

Hirtz, Alex, Lebourdais, Nolwenn, Rech, Fabien, Bailly, Yann, Vaginay, Athénaïs, Smaïl-Tabbone, Malika, Dubois-Pot-Schneider, Hélène, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
microtubule-targeting agent, QH301-705.5, proliferation, G-1, glioblastoma, Mitosis, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cyclopentanes, temozolomide, microtubule dynamics, Xenograft Model Antitumor Assays, Article, Receptors, G-Protein-Coupled, Gene Expression Regulation, Neoplastic, Mice, Receptors, Estrogen, Tubulin, Quinolines, Animals, Humans, Biology (General), Cell Proliferation, GPER agonist
Abstract

International audience; Glioblastoma (GBM) is the most common brain tumor in adults, which is very aggressive, with a very poor prognosis that affects men twice as much as women, suggesting that female hormones (estrogen) play a protective role. With an in silico approach, we highlighted that the expression of the membrane G-protein-coupled estrogen receptor (GPER) had an impact on GBM female patient survival. In this context, we explored for the first time the role of the GPER agonist G-1 on GBM cell proliferation. Our results suggested that G-1 exposure had a cytostatic effect, leading to reversible G2/M arrest, due to tubulin polymerization blockade during mitosis. However, the observed effect was independent of GPER. Interestingly, G-1 potentiated the efficacy of temozolomide, the current standard chemotherapy treatment, since the combination of both treatments led to prolonged mitotic arrest, even in a temozolomide less-sensitive cell line. In conclusion, our results suggested that G-1, in combination with standard chemotherapy, might be a promising way to limit the progression and aggressiveness of GBM.

Published
2021

6. Astrocytoma: A Hormone-Sensitive Tumor?

Author

Hirtz, Alex, Rech, Fabien, Dubois-Pot-Schneider, Hélène, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Receptors, Steroid, Sex Characteristics, glioblastoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, Models, Biological, Hormones, lcsh:Chemistry, lcsh:Biology (General), lcsh:QD1-999, gender, Disease Progression, Animals, Humans, Female, receptor isoforms, pregnancy, signaling, astrocytoma, lcsh:QH301-705.5, steroids, estrogens
Abstract

International audience; Astrocytomas and, in particular, their most severe form, glioblastoma, are the most aggressive primary brain tumors and those with the poorest vital prognosis. Standard treatment only slightly improves patient survival. Therefore, new therapies are needed. Very few risk factors have been clearly identified but many epidemiological studies have reported a higher incidence in men than women with a sex ratio of 1:4. Based on these observations, it has been proposed that the neurosteroids and especially the estrogens found in higher concentrations in women's brains could, in part, explain this difference. Estrogens can bind to nuclear or membrane receptors and potentially stimulate many different interconnected signaling pathways. The study of these receptors is even more complex since many isoforms are produced from each estrogen receptor encoding gene through alternative promoter usage or splicing, with each of them potentially having a specific role in the cell. The purpose of this review is to discuss recent data supporting the involvement of steroids during gliomagenesis and to focus on the potential neuroprotective role as well as the mechanisms of action of estrogens in gliomas.

Published
2020

9. Contributors

Author

Flament, Stéphane, primary, Chardard, Dominique, additional, Chesnel, Amand, additional, Dumond, Hélène, additional, Tsai, Pei-San, additional, Propper, Catherine R., additional, Aranzábal, Mari Carmen Uribe, additional, Sever, David M., additional, Staub, Nancy L., additional, Carr, James A., additional, Greven, Hartmut, additional, Woodley, Sarah K., additional, Rastogi, Rakesh K., additional, Polese, Gianluca, additional, D’Aniello, Biagio, additional, Pinelli, Claudia, additional, Chieffi-Baccari, Gabriella, additional, and Norris, David O., additional

Published
2011
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13. Apprentissage semi-supervisé pour la complétion de données biologiques

Author

Boukhobza, Taha, Clausel, Marianne, Dumond, Hélène, Thiébaut, Charlène, Thierry-Laumont, Romain, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Élie Cartan de Lorraine (IECL), Dumond, Helene, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [MATH.MATH-NA] Mathematics [math]/Numerical Analysis [math.NA], [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], ComputingMilieux_MISCELLANEOUS, [MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA]
Abstract

National audience

Published
2018

14. Regulation of ERα36 expression: a revamped network in the old story of breast tumors

Author

Thiébaut, Charlène, Chesnel, Amand, Chesnel, Maelle, Boukhobza, Taha, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), and Dumond, Helene

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2018

16. Lifelong testicular differentiation in Pleurodeles waltl (Amphibia, Caudata)

Author

Chesnel Amand, Chardard Dominique, Dumond Hélène, and Flament Stéphane

Subjects
Gynecology and obstetrics, RG1-991, Reproduction, QH471-489
Abstract

Abstract Background In numerous Caudata, the testis is known to differentiate new lobes at adulthood, leading to a multiple testis. The Iberian ribbed newt Pleurodeles waltl has been studied extensively as a model for sex determination and differentiation. However, the evolution of its testis after metamorphosis is poorly documented. Methods Testes were obtained from Pleurodeles waltl of different ages reared in our laboratory. Testis evolution was studied by several approaches: morphology, histology, immunohistochemistry and RT-PCR. Surgery was also employed to study testis regeneration. Results In this species, the testis is linked to the lung. This association consists of connective tissue derived from the mesorchium and the coelomic epithelium surrounding the lung and takes place at the end of larval life. This tissue contains lobules including primordial germ cells with a typical large and polylobular nucleus. The anterior part of the testis remains thin and undifferentiated while the posterior part differentiates in a large first testis lobe where spermatogenesis occurs during the first year of life. The undifferentiated status of the anterior part is attested by the lack of expression of the testis marker Dmrt1 and the meiosis entry marker Dmc1. Three-year-old Pleurodeles waltl possess multiple testes made up of two lobes. The second lobe appears at the caudal extremity of the first one from residual primordial germ cells located near or even inside efferent ducts in the glandular tissue that usually appears following spermatozoa extrusion. Surprisingly, in the case of surgical elimination of the anterior part of the testis, de novo spermatogenesis is stopped in the first lobe which becomes restricted to the glandular tissue. Following first testis lobe removal, the anterior part of the testis regenerates a new testis lobe, a process stimulated in the presence of DHT. Conclusion Pleurodeles waltl constitute an original gonochoristic vertebrate model in which testis differentiation is observed up to adulthood.

Published
2009
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17. L’expression d’ER$\alpha$36: un nouveau marqueur de transformation néoplasique et de progression tumorale mammaire ?

Author

Thiébault, Charlène, Morel, Chloé, Harlé, Alexandre, Chesnel, Amand, Chamard-Jovenin, Clémence, Boukhobza, Taha, Merlin, Jean-Louis, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, and Maquin, Didier

Subjects
[SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

18. Low-dose alkylphenol exposure promotes mammary epithelium alterations and transgenerational developmental defects, but does not enhance tumorigenic behaviour of breast cancer cells

Author

Chamard-Jovenin, Clémence, Thiébaut, Charlène, Chesnel, Amand, Bresso, Emmanuel, Morel, Chloé, Smaïl-Tabbone, Malika, Devignes, Marie-Dominique, Boukhobza, Taha, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Knowledge representation, reasonning (ORPAILLEUR), and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD)

Subjects
mammary gland, ERα36, [SDV.TOX]Life Sciences [q-bio]/Toxicology, cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, alkylphenol mix, estrogen receptor alpha 36, development, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract

International audience; Fetal and neonatal exposure to long chain alkylphenols has been suspected to promote breast developmental disorders and consequently to increase breast cancer risk. However, disease predisposition from developmental exposures remains unclear. In this work, human MCF-10A mammary epithelial cells were exposed in vitro to a low dose of a realistic [4-nonylphenol+4-tert-octylphenol] mixture. Transcriptome and cell phenotype analyses combined to functional and signaling network modeling indicated that long chain alkylphenols triggered enhanced proliferation, migration ability and apoptosis resistance and shed light on the underlying molecular mechanisms which involved the human estrogen receptor variant ERα36. A male mouse inherited transgenerational model of exposure to 3 environmentally relevant doses of the alkylphenol mix was set up in order to determine whether and how it would impact on mammary gland architecture. Mammary glands from F3 progeny obtained after intrabuccal chronic exposure of C57BL/6J P0 pregnant mice followed by F1 to F3 male inheritance displayed an altered histology which correlated with the phenotypes observed in vitro in human mammary epithelial cells. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant, such consequences of alkylphenol exposure could be extrapolated from mouse model to human. However, transient alkylphenol treatment combined to ERα36 overexpression in mammary epithelial cells were not sufficient to trigger tumorigenesis in xenografted Nude mice. Therefore, it remains to be determined if low dose alkylphenol transgenerational exposure and subsequent abnormal mammary gland development could account for an increased breast cancer susceptibility.

Published
2017

19. Validation de ER$\alpha$36 comme marqueur prédictif de susceptibilité aux nonylphénols in vivo et in vitro

Author

Chamard-Jovenin, Clémence, Thiébaut, Charlène, Chesnel, Amand, Bresso, Emmanuel, Morel, Chloé, Smaïl-Tabbone, Malika, Devignes, Marie-Dominique, Boukhobza, Taha, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Knowledge representation, reasonning (ORPAILLEUR), and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD)

Subjects
[SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2017

20. From ERα66 to ERα36: a new predictive marker for cancer progression and therapeutic response in breast tumors ?

Author

Thiébaut, Charlène, Morel, Chloé, Harlé, Alexandre, Chesnel, Amand, Leroux, Agnès, Chamard-Jovenin, Clémence, Boukhobza, Taha, Merlin, Jean-Louis, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, CGE, Dumond, Helene, Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and THIEBAUT, Charlène

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

21. Transgenerational effects of ERalpha36 over-expression on mammary gland development and molecular phenotype: clinical perspective for breast cancer risk and therapy

Author

Chamard-Jovenin, Clémence, Chesnel, Amand, Bresso, Emmanuel, Morel, Chloé, Thiébaut, Charlène, Smail-Tabbone, Malika, Djermoune, El-Hadi, Devignes, Marie-Dominique, Boukhobza, Taha, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Knowledge representation, reasonning (ORPAILLEUR), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Computational Algorithms for Protein Structures and Interactions (CAPSID), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract

International audience; Growing source of evidence suggests that exposure to estrogen mimicking agents is a risk factor for breast cancer onset and progression. Long chain alkylphenols are man made compounds still present in household products, industrial and agricultural processes, leading to a global environmental and human contamination. These molecules are known to exert estrogen -like activities through binding to classical estrogen receptors. Recently, we have demonstrated that a realistic mixture of 4 tert - octylphenol and 4 - nonylphenol can stimulate proliferation and modulate epigenetic status of testicular cancer germ cells through a rapid, Estrogen Receptor alpha 36 (ERα36) -dependent non genomic pathway (Ajj et al, 2013; doi: 10.1371/journal.pone.0061758). In a retrospective study of breast tumor samples, we also validated ERα36 expression as a reliable prognostic factor for cancer progression from an estrogen dependent prolifera tive tumor toward an estrogen dispensable metastatic disease (Chamard - Jovenin et al, 2015; doi: 10.1186/s12918 - 015 - 0178 - 7). Since high ERα36 expression enhances expression of migration/invasion markers in breast tumors, we addressed the question of its involvement in response to alkylphenol exposure in vitro (MCF -10A mammary epithelial cell line and MCF -7 estrogen -sensitive cancer cells) and in vivo ( C57BL mice). A male inherited transgenerational model of exposure to environmentally relevant doses of an alkylphenol mix was set up in C57BL/6J mice to determine whether and how it impacts on mammary gland morphogenesis. Human mammary epithelial MCF -10A cells were exposed to similar doses to decipher the molecular mechanisms involved by a combination of transcriptomic study, cell phenotype analyses, functional and signaling network modeling. The relevance of mouse phenotype extrapolation to human risk is discussed. Mouse mammary gland exposed transgenerationally to the alkylphenol mix displayed a neoplastic -like histology. This phenotype was correlated with the enhanced proliferation, migration ability and apoptosis resistance observed in vitro on human mammary epithelial cells and mediated by the estrogen receptor variant ERα36. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant , such consequences of alkylphenol exposure could be extrapolated from mouse model to human. Low dose alkylphenol transgenerational exposure could promote abnormal mammary gland development and subsequently increase the risk of breast cancer at ageing.

Published
2016

22. Long chain alkylphenol mixture promotes breast cancer initiation and progression through an ERα36-mediated mechanism

Author

Chamard-Jovenin, Clémence, Chesnel, Amand, Morel, Chloé, Devignes, Marie-Dominique, Smaïl-Tabbone, Malika, Boukhobza, Taha, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Knowledge representation, reasonning (ORPAILLEUR), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), and Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDE.MCG]Environmental Sciences/Global Changes, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology
Abstract

Présentation Poster; National audience; Growing source of evidence suggests that exposure to estrogen mimicking agents is a risk factor for breast cancer onset and progression. Long chain alkylphenols are man-made compounds still present in household products, industrial and agricultural processes, leading to a global environmental and human contamination. These molecules are known to exert estrogen-like activities through binding to classical estrogen receptors. Recently, we have demonstrated that a realistic mixture of 4-tert-octylphenol and 4-nonylphenol can stimulate proliferation and modulate epigenetic status of testicular cancer germ cells through a rapid, Estrogen Receptor alpha 36 (ERα36)- dependent non genomic pathway (Ajj et al, 2013; doi: 10.1371/journal.pone.0061758). In a retrospective study of breast tumor samples, we also validated ERα36 expression as a reliable prognostic factor for cancer progression from an estrogen dependent proliferative tumor toward an estrogen dispensable metastatic disease (Chamard-Jovenin et al, 2015; doi: 10.1186/s12918-015-0178-7). Since high ERα36 expression enhances expression of migration/invasion markers in breast tumors, we addressed the question of its involvement in response to alkylphenol exposure in vitro (MCF-10A mammary epithelial cell line and MCF-7 estrogen-sensitive cancer cells) and in vivo (C57/Bl6 mice). MethodsIn order to characterize the molecular events in alkylphenol exposed cells, ERα36 overexpression (knock in) or gene-silencing (knock down) strategies combined to microarray analyses of the mixture target genes were used in MCF-10A cells. Molecular and cellular biology experiments confirmed the predicted phenotypes. A customized database was designed to analyze comprehensive gene expression results, nonlinear correlation analyses, and mutual information computations helpful for the modeling of alkylphenol/ERα36-dependent pathways.In vivo, alkylphenol mixture doses, representative of human exposure, were orally given to C57/Bl6 pregnant females and histological analyses were then performed on F1 mammary glands. Key ResultsOur results highlight a key role for ERa36 in alkylphenol non genomic src protein kinase /PI3-kinase/serine-threonine kinase Akt/ nuclear factor-kappa B signaling in non cancerous epithelial breast cells. Flow cytometry analyses, scratch-wound assays and caspase clivage measurements indicate that the alkylphenol mixture may promote a neoplastic like phenotype, i. e. proliferation, apoptosis escape and migration in MCF-10A epithelial cells through an ERα36 dependent pathway. These results are currently used to build a model of alkylphenol-directed breast cancer induction and progression. In vivo, mammary gland hyperplasia is observed following alkylphenol exposure during embryonic life. ConclusionsHence, alkylphenol and/or ERa36-dependent control of the proliferation, adhesion and survival pathways opens the way to a better understanding of the link between endocrine disruptor exposure and the burden of hormone sensitive cancers. This work is supported by ANSES (n°2012-2-014).

Published
2016

23. Caractérisation du rôle des perturbateurs endocriniens sur des cellules épithéliales mammaires par classification et enrichissement de données

Author

Chamard-Jovenin, Clémence, Boukhobza, Taha, Dumond, Hélène, Dumond, Helene, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation Poster; National audience

Published
2016

25. From ERalpha66 to ERalpha36 : a new predcitive marker for cancer progression and therapeutic response in breast tumors

Author

Morel, Chloé, Harlé, Alexandre, Chesnel, Amand, Chamard-Jovenin, Clémence, Jung, Alain, Abecassis, Joseph, Leroux, Agnès, Boukhobza, Taha, Merlin, Jean-Louis, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, and Merlin, Jean-Louis

Subjects
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation Poster; National audience

Published
2015

26. Long chain alkylphenol mixture promotes breast cancer initiation and progression through an ERα36-mediated mechanism

Author

Chamard, Clémence, Chesnel, Amand, Djermoune, El-Hadi, Morel, Chloé, Boukhobza, Taha, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Dumond, Helene

Subjects
[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.CAN] Life Sciences [q-bio]/Cancer, alkylphenols, cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS, environnement
Abstract

National audience

Published
2015

27. Long chain alkyphenol mixture promotes breast cancer initiation and progression through an ER$\alpha$36-mediated mechanism

Author

Chamard-Jovenin, Clémence, Chesnel, Amand, Morel, Chloé, Devignes, Marie-Dominique, Smaïl-Tabbone, Malika, Boukobza, Taha, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Computational Algorithms for Protein Structures and Interactions (CAPSID), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Knowledge representation, reasonning (ORPAILLEUR), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation Poster; International audience

Published
2015

28. From ERα66 to ERα36: a generic method for validating a prognosis marker of breast tumor progression

Author

Chamard-Jovenin, Clémence, Jung, Alain C., Chesnel, Amand, Abecassis, Joseph, Flament, Stéphane, Ledrappier, Sonia, Macabre, Christine, Boukhobza, Taha, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Centre Paul Strauss, CRLCC Paul Strauss, and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Retrospective study, ERalpha36, Structural Biology, Modelling and Simulation, Applied Mathematics, Distance based tumor classification, Breast tumor, Gene network identification, [SDV.CAN]Life Sciences [q-bio]/Cancer, Molecular Biology, Metastatic potential, Nonlinear correlation, [SPI.AUTO]Engineering Sciences [physics]/Automatic
Abstract

International audience; Background: Estrogen receptor alpha36 (ERalpha36), a variant of estrogen receptor alpha (ER) is expressed in about half of breast tumors, independently of the [ER+]/[ER-] status. In vitro, ERalpha36 triggers mitogenic non-genomic signaling and migration ability in response to 17beta-estradiol and tamoxifen. In vivo, highly ERalpha36 expressing tumors are of poor outcome especially as [ER+] tumors are submitted to tamoxifen treatment which, in turn, enhances ERalpha36 expression. Results: Our study aimed to validate ERalpha36 expression as a reliable prognostic factor for cancer progression from an estrogen dependent proliferative tumor toward an estrogen dispensable metastatic disease. In a retrospective study, we tried to decipher underlying mechanisms of cancer progression by using an original modeling of the relationships between ERalpha36, other estrogen and growth factor receptors and metastatic marker expression. Nonlinear correlation analyses and mutual information computations led to characterize a complex network connecting ERalpha36 to either non-genomic estrogen signaling or to metastatic process. Conclusions: This study identifies ERalpha36 expression level as a relevant classifier which should be taken into account for breast tumors clinical characterization and [ER+] tumor treatment orientation, using a generic approach for the rapid, cheap and relevant evaluation of any candidate gene expression as a predictor of a complex biological process.

Published
2015

29. An alkylphenol mix promotes proliferation of seminoma-like TCam-2 cell line through ERalpha36-dependent mechanisms

Author

Chamard-Jovenin, Clémence, Ajj, Hussein, Pinel, Sophie, Chesnel, Amand, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), ANSES, Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Dumond, Helene

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation poster; International audience

Published
2014

30. Long chain alkylphenol mixture promotes mammary epithelial cell metaplastic phenotype through an ERalpha36-mediated mechanism

Author

Chamard, Clémence, Bresso, Emmanuel, Boukobza, Taha, Devignes, Marie-Dominique, Smaïl-Tabbone, Malika, Chesnel, Amand, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Knowledge representation, reasonning (ORPAILLEUR), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), and Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation Poster; National audience

Published
2014

31. Long chain alkylphenol mixture promotes mammary epithelial cell metaplastic phenotype through an estrogen receptor alpha 36 mediated mechanism

Author

Chamard, Clémence, Bresso, Emmanuel, Boukhobza, Taha, Devignes, Marie-Dominique, Smaïl-Tabbone, Malika, Chesnel, Amand, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Knowledge representation, reasonning (ORPAILLEUR), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation Poster; International audience

Published
2014

32. From ERα66 to ERα36: a new predictive marker for cancer progression and therapeutic response in breast tumors ?

Author

Chamard, Clémence, Jung, Alain, Chesnel, Amand, Abecassis, Joseph, Flament, Stéphane, Ledrappier, Sonia, Macabre, Christine, Boukhobza, Taha, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, CRLCC Paul Strauss, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation Poster; International audience

Published
2014

33. ERalpha36, un marqueur prédictif de la réponse thérapeutique et du potentiel métastatique des tumeurs mammaires ?

Author

Chamard, Clémence, Jung, Alain, Boukhobza, Taha, Abecassis, Joseph, Flament, Stéphane, Ledrappier, Sonia, Macabre, Christine, Chesnel, Amand, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Centre Paul Strauss, CRLCC Paul Strauss, Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Dumond, Helene

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation Poster; National audience

Published
2014

34. ERα36:un nouveau marqueur prédictif de la progression metastatique des tumeurs mammaires

Author

Chamard-Jovenin, Clémence, Jung, Alain, Chesnel, Amand, Abecassis, Joseph, Flament, Stéphane, Ledrappier, Sonia, Macabre, Christine, Boukhobza, Taha, Dumond, Hélène, Dumond, Helene, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, CRLCC Paul Strauss, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2014

35. ERα36, un marqueur prédictif de la réponse thérapeutique et du potentiel métastatique des tumeurs mammaires ?

Author

Chamard, Clémence, Jung, Alain, Boukhobza, Taha, Abecassis, Joseph, Flament, Stéphane, Ledrappier, Sonia, Macabre, Christine, Chesnel, Amand, Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, CRLCC Paul Strauss, and Dumond, Helene

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation Poster; National audience

Published
2013

36. Steroid hormones and endocrine disruptors for gonad development and carcinogenesis

Author

Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine, Denyse Bagrel, and Dumond, Helene

Subjects
cellules germinales, [SDV.CAN] Life Sciences [q-bio]/Cancer, estrogènes, developpement, steroides, reproduction cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

Au cours de mon doctorat puis de mes différents stages post-doctoraux, j'ai développé des approches de physiologie et génomique comparatives pour identifier et caractériser des médiateurs moléculaires impliqués dans le contrôle de la prolifération des cellules eucaryotes en réponse aux variations de l'environnement. Je me suis également attachée, dans des modèles biologiques divers, à replacer les mécanismes moléculaires et cellulaires étudiés dans un contexte plus général de physiologie de l'organisme. Depuis ma nomination en tant que Maître de Conférences à l'Université Nancy 1, je me suis focalisée sur l'influence des hormones stéroïdes sur la prolifération et la différenciation normale ou pathologique des cellules germinales. Le projet de recherche que je souhaite développer s'articule autour de 3 mots-clefs : tumeurs hormono-sensibles, perturbateurs endocriniens, voie non conventionnelle de signalisation oestrogénique. Le premier axe renferme un projet concernant les effets d'un mélange d'alkylphénols sur l'initiation et la progression tumorale dans un modèle de cancer testiculaire d'origine germinale puis de cancer mammaire, in vitro et in vivo. Le but est de caractériser le rôle éventuel de ERa36 dans ces processus afin de valider cette forme du récepteur des oestrogènes comme marqueur d'exposition aux perturbateurs endocriniens dans les cellules hormono-. Le second axe s'inscrit dans un objectif à plus long terme qui sera de valider ERa36 comme marqueur prédictif de réponse aux traitements anti-tumoraux dans les cancers hormono-sensibles et en particulier dans le cancer du sein.

Published
2013

37. Hormones stéroïdes et perturbateurs endocriniens dans le développement gonadique et la cancérogenèse

Author

Dumond, Hélène, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Université de Lorraine, and Denyse Bagrel

Subjects
cellules germinales, estrogènes, developpement, steroides, reproduction cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

Au cours de mon doctorat puis de mes différents stages post-doctoraux, j'ai développé des approches de physiologie et génomique comparatives pour identifier et caractériser des médiateurs moléculaires impliqués dans le contrôle de la prolifération des cellules eucaryotes en réponse aux variations de l'environnement. Je me suis également attachée, dans des modèles biologiques divers, à replacer les mécanismes moléculaires et cellulaires étudiés dans un contexte plus général de physiologie de l'organisme. Depuis ma nomination en tant que Maître de Conférences à l'Université Nancy 1, je me suis focalisée sur l'influence des hormones stéroïdes sur la prolifération et la différenciation normale ou pathologique des cellules germinales. Le projet de recherche que je souhaite développer s'articule autour de 3 mots-clefs : tumeurs hormono-sensibles, perturbateurs endocriniens, voie non conventionnelle de signalisation oestrogénique. Le premier axe renferme un projet concernant les effets d'un mélange d'alkylphénols sur l'initiation et la progression tumorale dans un modèle de cancer testiculaire d'origine germinale puis de cancer mammaire, in vitro et in vivo. Le but est de caractériser le rôle éventuel de ERa36 dans ces processus afin de valider cette forme du récepteur des oestrogènes comme marqueur d'exposition aux perturbateurs endocriniens dans les cellules hormono-. Le second axe s'inscrit dans un objectif à plus long terme qui sera de valider ERa36 comme marqueur prédictif de réponse aux traitements anti-tumoraux dans les cancers hormono-sensibles et en particulier dans le cancer du sein.

Published
2013

38. From ERα66 to ERα36, a new marker for breast tumor therapeutic response ?

Author

Chamard, Clémence, Jung, Alain, Chesnel, Amand, Abecassis, Joseph, Flament, Stéphane, Ledrappier, Sonia, Macabre, Christine, Boukhobza, Taha, Dumond, Hélène, Dumond, Helene, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, CRLCC Paul Strauss, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)

Subjects
[SPI.AUTO] Engineering Sciences [physics]/Automatic, [SPI.AUTO]Engineering Sciences [physics]/Automatic
Abstract

National audience; Breast cancer is the main cause of cancer-induced morbidity and mortality in women. Breast tumors are usually classified according to their ERa66 status. Such a classification led to the use of endocrine therapeutic agents against ER-positive tumors [ER+]. Nevertheless, numerous therapeutic failures are observed due to unclear resistance mechanism. ERa66 was considered as the unique functional estrogen receptor in hormone sensitive breast tumor until the recent identification of membrane bound new estrogen receptors: the G protein coupled estrogen receptor (GPER) and the 36kDa ERa splice variant (ERa36). Surprisingly, ERa36 stimulates cell proliferation in response to tamoxifen treatment and could therefore be involved in the acquired resistance to this compound. Moreover, a high ERa36 expression level correlates with a short term survival for ERa66-negative patients as well as enhanced tumorigenesis and metastatic potential of triple-negative cells in vitro. The aim of our project was to improve the classification of so-called "ER-positive" breast tumors by taking into account the key role of ERa36 and GPER in the control of non genomic estrogen response and metastatic potential. We set up a retrospective study, performed on hundreds of breast tumor samples, in order to better define the field of acceptance of [ER+] versus [ER-] classification and to help the clinicians choosing the best therapeutic compounds. We addressed two main questions: 1- Are ERa36 and GPER predictive markers of therapeutic response in ER-positive tamoxifen-treated patients [ER+,TAM+]? 2- Is a high ERa36 or/and GPER expression level of poor prognosis because these receptors stimulate tumor progression and metastatic potential? ERa36, GPER and metastatic marker expressions were measured by real-time PCR in almost 100 [ER+,TAM] as well as 60 triple-negatives [ER-,TAM-] tumor samples. Then, we performed statistical analyses between gene expression levels and clinical parameters (grade, survival, treatment). Modeling of the potential relationship between the genes tested using nonlinear correlation analyses, Bayesian inference and transfer entropy computation led to the characterization of complex network connecting non genomic estrogen signaling and metastatic process. Hence, ERa36 expression is strongly related to GPER, Snail1, Vim and MMP9A in [ER+, TAM+] samples. This suggests that, after tamoxifen treatment, ERa36 may stimulate the metastatic potential of [ER+] tumor in vivo. Such a model will be first tested in vitro in hormone-dependent or triple negative cell lines. Taken together, the results from this project should lead to (i) a better understanding of the breast tumor hormone sensitive status, (ii) a validation of new predictive markers of response in order to improve therapeutic orientation, (iii) the potential discovery of new therapeutic targets in triple-negative tumors.

Published
2013

39. From here to ERalpha36, a new predictive marker for breast tumor therapeutic response ?

Author

Chamard, Clémence, Dumond, Hélène, Jung, Alain, Chesnel, Amand, Macabre, Christine, Flament, Stéphane, Ledrappier, Sonia, Abecassis, Joseph, Boukhobza, Taha, Dumond, Helene, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Paul Strauss, and CRLCC Paul Strauss

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Présentation Poster; International audience

Published
2013

40. Influence des micropolluants en mélange sur la croissance de tumeurs testiculaires d'origine germinale

Author

Wallacides, Angelina, Ajj, Hussein, Pinel, Sophie, Chesnel, Amand, Dumond, Hélène, Dumond, Helene, Centre de Recherche en Automatique de Nancy (CRAN), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

National audience; Au cours des trente dernières années, les observateurs constatent un doublement des cas de cancer testiculaire chez les jeunes adultes dans les pays industrialisés. Ces altérations semblent dues à l'exposition à des xénobiotiques d'origines diverses, regroupés sous l'appellation de perturbateurs endocriniens. Chez les individus exposés dès la vie fœtale à des composés chimiques analogues possédant une activité estrogénique ou anti-androgénique, on observe un arrêt ou une modification du processus de différenciation des cellules germinales qui peuvent conduire au développement de pré-carcinome in situ (CIS). Notre hypothèse est que, chez le jeune adulte, sous l'effet de stéroïdes et de perturbateurs endocriniens, les cellules de CIS prolifèrent et forment des tumeurs testiculaires.

Published
2013

41. Influence des alkylphénols sur la croissance de tumeurs testiculaires d'origine germinale

Author

Ajj, Hussein, Chesnel, Amand, Pinel, Sophie, Flayac, Justine, Flament, Stéphane, Dumond, Hélène, Maquin, Didier, Signalisation, Génomique et Recherche Translationnelle en Oncologie (SIGRETO), Université Henri Poincaré - Nancy 1 (UHP), Centre de Recherche en Automatique de Nancy (CRAN), and Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2012

42. Estrogens and alkylphenols promote proliferation of the seminoma-like TCam-2 cell line through ERα36-dependent pathways

Author

Ajj, Hussein, Pinel, Sophie, Flament, Stéphane, Chesnel, Amand, Dumond, Hélène, and Dumond, Helene

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer
Abstract

Background Seminoma, originated from carcinoma in situ cells (CIS), is one of the main causes of cancer in young men. Postpubertal development of these testicular germ cell tumors suggests a hormone-sensitive way of CIS cell proliferation induction probably stimulated by lifelong exposure to endocrine disruptors. In a first step to understand the mechanisms underlying the deleterious effects of endocrine disrupting compounds on germ cells, we aimed to decipher the estrogen-dependent transduction pathways in TCam2 cells. Then, we began to assess the effects of a [4tert-octyl + 4-nonylphenol] mix on testicular germ cell tumors in vitro and in vivo. Material and methods In this study, we used the unique seminoma TCam-2 cell line which do not express the canonical ER66 estrogen receptor but ERα36, a truncated isoform retaining the DNA-binding, partial dimerisation and ligand-binding domains and a specific C-term 27 aa sequence. Cells were exposed to either estradiol at concentrations in the range of those detected in an adult human testis or to a [4tert-octyl + 4-nonylphenol] mix used at low doses - i.e. those found in food and drinking water. In vitro, we performed cell proliferation assays, siRNA- or shRNA-directed knockdown, microarray-directed gene targeting and signaling pathways identification after short term (1h) or mid-term (24h or 48h) treatment. We also addressed the question of TCam-2 derived tumor growth in xenografted Nude mice treated with the [4tert-octyl + 4-nonylphenol] mix. Results We demonstrate in vitro that estradiol and the alkylphenol mix trigger TCam-2 cell proliferation through ER36-dependent pathways. We establish that estradiol can activate GPER-cAMP/PKA signaling pathway. Stable ERα36 knockdown indicates that ERα36 is (i) necessary for cell proliferation (ii) a downstream target of estradiol-activated GPER/PKA/CREB pathway, (iii) required for estradiol-dependent EGFR expression. The [4tert-octyl + 4-nonylphenol] mix signaling pathway is clearly ER36 dependent but seems to be partially non-estrogenic. Finally, we show that the [4tert-octyl + 4-nonylphenol] mix stimulates tumor growth in TCam-2 xenografted Nude mice. Conclusions Our results highlight the functional role of ERα36 in context of seminoma cell proliferation and the importance of testing ERα36 in vivo as a possible marker for endocrine disruptor susceptibility.

Published
2012

43. Influence d'un mélange d'alkylphénols sur la croissance de tumeurs testiculaires d'origine germinale

Author

Ajj, Hussein, Chesnel, Amand, Pinel, Sophie, Flayac, Justine, Flament, Stéphane, Dumond, Hélène, Maquin, Didier, Signalisation, Génomique et Recherche Translationnelle en Oncologie (SIGRETO), Université Henri Poincaré - Nancy 1 (UHP), Centre de Recherche en Automatique de Nancy (CRAN), and Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMethodologies_GENERAL, ComputingMilieux_MISCELLANEOUS
Abstract

Session Poster; National audience

Published
2011

47. PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression

Author

Augustin, Angélique, primary, Spenlehauer, Catherine, additional, Dumond, Hélène, additional, Ménissier-de Murcia, Josiane, additional, Piel, Matthieu, additional, Schmit, Anne-Catherine, additional, Apiou, Françoise, additional, Vonesch, Jean-Luc, additional, Kock, Michael, additional, Bornens, Michel, additional, and de Murcia, Gilbert, additional

Published
2003
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49. Temporal and Spatial SOX9 Expression Patterns in the Course of Gonad Development of the Caudate Amphibian Pleurodeles waltl.

Author

DUMOND, HÉLÈNE, AL-ASAAD, IMANE, CHESNEL, AMAND, CHARDARD, DOMINIQUE, BOIZET-BONHOURE, BRIGITFE, FLAMENT, STÉPHANE, and KUNTZ, SANDRA

Subjects
PLEURODELES waltl, AMNIOTES, GONADS, PROTEINS, ZOOLOGY
Abstract

The article presents a study on Pleurodeles waltl, a species that displays a ZZ/ZW genetic mode of sex determination and a temperature-dependent mechanism of female-to-male sex reversal. It was found that the deduced protein segregates from the group of anuran and could be more closely associated with amniote. The results indicate that in Pleurodeles waltl, the SOX family of transcription factors could play a role during the late phase of gonad differentiation instead of sex determination.

Published
2011
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50. Lifelong testicular differentiation in Pleurodeles waltl (Amphibia, Caudata).

Author

Flament, Stéphane, Dumond, Hélène, Chardard, Dominique, and Chesnel, Amand

Subjects
*PLEURODELES waltl, *SALAMANDERS, *TESTIS, *SEX differentiation (Embryology), *SEXING of animals, *GERM cells
Abstract

Background: In numerous Caudata, the testis is known to differentiate new lobes at adulthood, leading to a multiple testis. The Iberian ribbed newt Pleurodeles waltl has been studied extensively as a model for sex determination and differentiation. However, the evolution of its testis after metamorphosis is poorly documented. Methods: Testes were obtained from Pleurodeles waltl of different ages reared in our laboratory. Testis evolution was studied by several approaches: morphology, histology, immunohistochemistry and RT-PCR. Surgery was also employed to study testis regeneration. Results: In this species, the testis is linked to the lung. This association consists of connective tissue derived from the mesorchium and the coelomic epithelium surrounding the lung and takes place at the end of larval life. This tissue contains lobules including primordial germ cells with a typical large and polylobular nucleus. The anterior part of the testis remains thin and undifferentiated while the posterior part differentiates in a large first testis lobe where spermatogenesis occurs during the first year of life. The undifferentiated status of the anterior part is attested by the lack of expression of the testis marker Dmrt1 and the meiosis entry marker Dmc1. Three-year-old Pleurodeles waltl possess multiple testes made up of two lobes. The second lobe appears at the caudal extremity of the first one from residual primordial germ cells located near or even inside efferent ducts in the glandular tissue that usually appears following spermatozoa extrusion. Surprisingly, in the case of surgical elimination of the anterior part of the testis, de novo spermatogenesis is stopped in the first lobe which becomes restricted to the glandular tissue. Following first testis lobe removal, the anterior part of the testis regenerates a new testis lobe, a process stimulated in the presence of DHT. Conclusion: Pleurodeles waltl constitute an original gonochoristic vertebrate model in which testis differentiation is observed up to adulthood. [ABSTRACT FROM AUTHOR]

Published
2009
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