ER-α36, a Variant of ER-α, Promotes Tamoxifen Agonist Action in Endometrial Cancer Cells via the MAPKERK and PI3KAkt Pathways 英文参考文献.docVIP

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ER-α36, a Variant of ER-α, Promotes Tamoxifen Agonist Action in Endometrial Cancer Cells via the MAPKERK and PI3KAkt Pathways 英文参考文献.doc

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ER-α36, a Variant of ER-α, Promotes Tamoxifen Agonist Action in Endometrial Cancer Cells via the MAPKERK and PI3KAkt Pathways 英文参考文献

ER-a36,aVariantofER-a,PromotesTamoxifenAgonist ActioninEndometrialCancerCellsviatheMAPK/ERK andPI3K/AktPathways Sheng-LiLin1,Li-YingYan2,Xin-TianZhang3,JuYuan1,MoLi1,JieQiao2*,Zhao-YiWang3* ,Qing-Yuan Sun1* 1StateKeyLaboratoryofReproductiveBiology,InstituteofZoology,ChineseAcademyofSciencesandGraduateSchool,ChineseAcademyofSciences,Beijing,China, 2CenterofReproductiveMedicine,DepartmentofObstetricsandGynecology,PekingUniversityThirdHospital,Beijing,China,3DepartmentofMedicalMicrobiologyand Immunology,CreightonUniversityMedicalSchool,Omaha,Nebraska,UnitedStatesofAmerica Abstract Background:Recently,anovelvariantofER-a,ER-a36wasidentifiedandcloned.ER-a36lacksintrinsictranscriptionactivity and mainly mediates nongenomic estrogen signaling. Here, we studied the role of nongenomic estrogen signaling pathwaysmediatedbyER-a36intamoxifenresistanceandagonistaction. Methodology: The cellular localization of ER-a36 was examined by immunofluorescence in MCF-7 cells and Hec1A cells. MCF-7breastcancercells,MCF-7cellsexpressingrecombinantER-a36(MCF-7/ER36),Hec1Aendometrialcancercellsand Hec1AcellswithsiRNAknockdownofER-a36(Hec1A/RNAiER36)weretreatedwith17b-estradial(E2)andtamoxifen(TAM) intheabsenceandpresenceofkinaseinhibitorU0126andLY294002.Weexaminedphosphorylationofsignalingmolecules andtheexpressionofc-Mycbyimmunoblotting,andtumorcellgrowthbyMTTassay. Conclusions: ER variant ER-a36 enhances TAM agonist activity through activation of the membrane-initiated signaling pathwaysinendometrialcancer,andthatER-a36isinvolvedindenovoandacquiredTAMresistanceinbreastcancer. Citation:LinS-L,YanL-Y,ZhangX-T,YuanJ,LiM,etal.(2010)ER-a36,aVariantofER-a,PromotesTamoxifenAgonistActioninEndometrialCancerCellsviathe MAPK/ERKandPI3K/AktPathways.PLoSONE5(2):e9013.doi:10.1371/journal.pone.0009013 Editor:SyedA.Aziz,HealthCanada,Canada ReceivedDecember11,2009;AcceptedJanuary13,2010;PublishedFebruary2,2010 Copyright:?2010Linetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAt