Progression of Mouse Skin Carcinogenesis Is Associated with Increased Erα Levels and Is Repressed by a Dominant Negative Form of Erα 英文参考文献.docVIP

Progression of Mouse Skin Carcinogenesis Is Associated with Increased Erα Levels and Is Repressed by a Dominant Negative Form of Erα 英文参考文献.doc

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Progression of Mouse Skin Carcinogenesis Is Associated with Increased Erα Levels and Is Repressed by a Dominant Negative Form of Erα 英文参考文献

ProgressionofMouseSkinCarcinogenesisIsAssociated withIncreasedEraLevelsandIsRepressedbya DominantNegativeFormofEra StellaLogotheti1.,DimitraPapaevangeliou1.,IoannisMichalopoulos2,MariaSideridou3, KaterinaTsimaratou3,IoannisChristodoulou1,KaterinaPyrillou1,VassilisGorgoulis3, SpirosVlahopoulos1,VassilisZoumpourlis1* 1BiomedicalApplications Unit, Institute ofBiology, Medicinal Chemistryand Biotechnology, NationalHellenic ResearchFoundation, Athens,Greece, 2Cryobiologyof Stem Cells, Centre of Immunology Transplantation, Biomedical Research Foundation, Academy of Athens, Athens, Greece, 3Molecular Carcinogenesis Group, DepartmentofHistologyandEmbryology,MedicalSchool,UniversityofAthens,Athens,Greece Abstract Estrogen receptors (ER), namely ERa and ERb, are hormone-activated transcription factors with an important role in carcinogenesis. In the present study, we aimed at elucidating the implication of ERa in skin cancer, using chemically- induced mouse skin tumours, as well as cell lines representing distinct stages of mouse skin oncogenesis. First, using immunohistochemical staining we showed that ERa is markedly increased in aggressive mouse skin tumours in vivo as comparedtothepapillomatumours,whereasERblevelsarelowandbecomeevenlowerintheaggressivespindletumours ofcarcinogen-treatedmice.Then,usingthemultistagemouseskincarcinogenesismodel,weshowedthatERagradually increasesduringpromotionandprogressionstagesofmouseskincarcinogenesis,peakingatthemostaggressivestage, whereasERblevelsonlyslightlychangethroughoutskincarcinogenesis.Stabletransfectionoftheaggressive,spindleCarB cells with a dominant negative form of ERa (dnERa) resulted in reduced ERa levels and reduced binding to estrogen responsiveelements(ERE)-containingsequences.WecharacterizedtwohighlyconservedEREsonthemouseERapromoter throughwhichdnERadecreasedendogenousERalevels.ThednERa-transfectedCarBcellspresentedalteredproteinlevels of cytoskeletal and cell adhesion molecules, slower growth rate and impaired an

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