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1、Leukemia&Lymphoma,February2011;52(2):298309ORIGINALARTICLE:RESEARCHWAVE1regulatesP-glycoproteinexpressionviaEzrininleukemiacells1111,42MING-HUAYANG,MING-YIZHAO,ZHUOWANG,RUIKANG,YU-LEIHE,3111XIAO-CHENGYIN,LI-YINGLIU,LIANG-CHUNYANG,CAI-XIAZHAN,541XIU-SHANWU,DAO-LINTANG,&LI-ZHICAO1Departme
2、ntofPediatrics,XiangyaHospital,CentralSouthUniversity,Changsha,HunanProvince,PeoplesRepublicof23China,ChildrensHospitalofChengdou,Chengdu,SichuanProvince,PeoplesRepublicofChina,DepartmentofPediatrics,4TheFirstAffiliatedHospitalofNanhuaUniversity,Hengyang,HunanProvince,PeoplesRepublicofCh
3、ina,HillmanCancer5Center,UniversityofPittsburghCancerInstitute,Pittsburgh,Pennsylvania,USA,andCollegeofLifeSciences,HunanNormalUniversity,Changsha,HunanProvince,PeoplesRepublicofChina(Received5September2010;revised1November2010;accepted4November2010)AbstractForchildrenwithacutemyeloblas
4、ticleukemia(AML),multidrugresistance(MDR)reducestreatmenteffectiveness,andoftenleadstopoorpatientsurvival.WhileanumberoffactorshavebeendescribedthataffectMDR,themechanismsunderlyingthiseffectremainunclear.Inthisstudy,theroleofWAVE1inMDRwasinvestigated.Among62childrenwithAML,highlevelsof
5、WAVE1wereassociatedwithpoorpatientoutcomes.ProteomictechniqueswereusedtoidentifynovelWAVE1-interactingproteinsfromleukemiacells,oneofwhichwasthecytoskeletonregulatorEzrin.Inleukemiacells,Forpersonaluseonly.WAVE1co-localizedwithbothEzrinandP-glycoprotein(P-gp),acriticalregulatoroftheMDRp
6、henotype.OverexpressionofWAVE1inK562leukemiacellsup-regulatedP-gpandEzrin,andreducedK562cellssensitivitytothechemotherapydrugadriamycin.TheoppositeeffectwasseenwhenWAVE1expressionwasreducedviaRNAinterference.Critically,overexpressionofWAVE1intheabsenceofEzrindidnotaffectP-gplevelsorMDR.
7、ThesedatasuggestthatWAVE1affectsP-gpandMDRofleukemiacellsthroughEzrin.Keywords:WAVE1,drugresistance,Ezrin,P-glycoproteinWAVE1coordinatescelldeathandglycolysis[7].IntroductionWehavepreviouslydemonstratedthatWAVE1isTheWiskottAldrichsyndromefamilyofproteins,overexpressedinbloodcan
