CD146 Expression in Human Breast Cancer Cell Lines Induces Phenotypic and Functional Changes Observed in Epithelial to Mesenchymal Transition 英文参考文献.docVIP

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CD146 Expression in Human Breast Cancer Cell Lines Induces Phenotypic and Functional Changes Observed in Epithelial to Mesenchymal Transition 英文参考文献.doc

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CD146 Expression in Human Breast Cancer Cell Lines Induces Phenotypic and Functional Changes Observed in Epithelial to Mesenchymal Transition 英文参考文献

CD146ExpressioninHumanBreastCancerCellLines InducesPhenotypicandFunctionalChangesObservedin EpithelialtoMesenchymalTransition Anne-MarieImbert1,2*,CelineGarulli1,2,ElodieChoquet2,3,MyriamKoubi2,3,MichelAurrand-Lions3,4 , ChristianChabannon1,2,3 1InstitutPaoli-Calmettes,CentredeRessourcesBiologiquesenOncologie,CentredeThe′rapie Cellulaire,Marseille,France,2Inserm,UMR1068,CentredeRechercheen Cance′rologiedeMarseille(CRCM),EquipeRechercheClinique,Marseille,France,3Universite′d’Aix-Marseille,Marseille,France,4Inserm,UMR1068,CentredeRechercheen Cance′rologiedeMarseille(CRCM),EquipeMole′cules d’Adhe′sionetInteractionsHo?te–Tumeur,Marseille,France Abstract Background:Metastasisisanimportantstepintumorprogressionleadingtoadisseminatedandoftenincurabledisease. Firststepsofmetastasisincludedown-regulationofcelladhesionmolecules,alterationofcellpolarityandreorganizationof cytoskeleton,modificationsassociatedwithenhancedmigratorypropertiesandresistanceoftumorcellstoanoikis.Such modificationsresembleEpithelialtoMesenchymalTransition(EMT).InbreastcancerCD146expressionisassociatedwith poorprognosisandenhancedmotility. Methodology/PrincipalFindings:On4differenthumanbreastcancercelllines,wemodifiedCD146expressioneitherwith shRNA technology in CD146 positive cells or with stable transfection of CD146 in negative cells. Modifications in morphology,growthandmigrationwereevaluated.UsingQ-RT-PCR,weanalyzedtheexpressionofdifferentEMTmarkers. We demonstrate that high levels of CD146 are associated with loss of cell-cell contacts, expression of EMT markers, increasedcellmotilityandincreasedresistancetodoxorubicinordocetaxel.ExperimentalmodulationofCD146expression induces changes consistent with the above described characteristics: morphology, motility, growth in anchorage independent conditions and Slug mRNA variations are strictly correlated with CD146 expression. These changes are associatedwithmodificationsofER(estrogenreceptor)andErbreceptorsandareenhancedbysimultaneousandopp