Expression of Erk5 in Early Stage Breast Cancer and Association with Disease Free Survival Identifies this Kinase as a Potential Therapeutic Target 英文参考文献.docVIP

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Expression of Erk5 in Early Stage Breast Cancer and Association with Disease Free Survival Identifies this Kinase as a Potential Therapeutic Target 英文参考文献.doc

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Expression of Erk5 in Early Stage Breast Cancer and Association with Disease Free Survival Identifies this Kinase as a Potential Therapeutic Target 英文参考文献

ExpressionofErk5inEarlyStageBreastCancerand AssociationwithDiseaseFreeSurvivalIdentifiesthis KinaseasaPotentialTherapeuticTarget JuanCarlosMontero1.,AlbertoOcan?a2.,MarAbad3,Mar?′aJesu′sOrtiz-Ruiz1,AtanasioPandiella1, AzucenaEspar?′s-Ogando1* 1Instituto de Biolog?′a Molecular y Celular del Ca′ncer, CSIC-Universidad de Salamanca, Salamanca, Spain, 2Oncology Service and AECC Unit, Complejo Hospitalario UniversitariodeAlbacete,Albacete,Spain,3DepartmentofPathology,HospitalUniversitariodeSalamanca,Salamanca,Spain Abstract Background: Breast cancer is the most common neoplasia in women. Even though advances in its treatment have improveddiseaseoutcome,somepatientsrelapse.Therefore,attemptstobetterdefinethemoleculardeterminantsthat drivebreastcancercellproliferationmayhelpindefiningpotentialtherapeutictargets.Mitogen-activatedproteinkinases (MAPK)playimportantrolesintumorigenesis.Oneofthem,Erk5,hasbeenlinkedtotheproliferationofbreastcancercells invitro.HerewehaveinvestigatedtheexpressionandprognosticvalueofErk5inhumanbreastcancer. Methodology/PrincipalFindings:AnimalandcellularmodelswereusedtostudyErk5expressionandfunctioninbreast cancer.In84humanbreasttumourstheexpressionofErk5wasanalyzedbyimmunohistochemistry.ActiveErk5(pErk5)was studiedbyWesternblotting.CorrelationofErk5withclinicopathologicalparametersandwithdisease-freesurvivalinearly stagebreastcancerpatientswasanalyzed.ExpressionofErk5wasdetectedinmostpatients,andoverexpressionwasfound in20%.ActiveErk5waspresentinasubstantialnumberofsamples,aswellasintumoursfromananimalbreastcancer model.OverexpressionofErk5wasassociatedwithadecreaseindisease-freesurvivaltime,whichwasindependentofother clinicopathological parameters of prognosis. Transient transfection of a short hairpin RNA (shRNA) targeting Erk5, and a stablecelllineexpressing adominantnegativeformofErk5(Erk5AEF),wereusedtoinvestigatetheinfluenceofErk5on drugsusedintheclinictotreatbreasttumours.WefoundthatinhibitionofErk5decreasedcancercellproliferationandalso