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1、npgYanZhangetal.CellResearch(2007)17:363-373npg363©2007IBCB,SIBS,CASAllrightsreserved1001-0602/07$30.00ORIGINALARTICLEwww.nature.com/crPGC-1αinducesapoptosisinhumanepithelialovariancancercellsthroughaPPARγ-dependentpathway1,*2,*111222YanZhang,YiBa,ChangLiu,GuoxunSun,LiDing,Songyu
2、anGao,JihuiHao,ZhentaoYu,Junfeng11211Zhang,KeZen,ZhongshengTong,YangXiang,Chen-YuZhang12StateKeyLaboratoryofPharmaceuticalBiotechnology,SchoolofLifeSciences,NanjingUniversity,Nanjing210093,China;TianjinMedicalUniversityCancerInstituteandHospital,Tianjin300060,ChinaPeroxisomeproli
3、ferator-activatedreceptorgamma(PPARγ)coactivator-1alpha(PGC-1α)coactivatesmultipletranscriptionfactorsandregulatesseveralmetabolicprocesses.ThecurrentstudyinvestigatedtheroleofPGC-1αintheinductionofapoptosisinhumanepithelialovariancancercells.ThePGC-1αmRNAlevelbetweenhumanovaries
4、andhumanovarianepithelialtumorswasexaminedbyquantitativeRT-PCR.LessPGC-1αexpressionwasfoundinthesurfaceepitheliumofmalignanttumorscomparedwithnormalovaries.OverexpressionofPGC-1αinhumanepithelialovariancancercelllineHo-8910inducedcellapoptosisthroughthecoordinatedregulationofBcl-
5、2andBaxexpres-sion.MicroarrayanalysesconfirmedthatPGC-1αdramaticallyaffectedtheapoptosis-relatedgenesinHo-8910cells.Mitochondrialfunctionalassayshowedthattheinductionofapoptosiswasthroughtheterminalstagebythereleaseofcytochromec.Furthermore,PGC-1α-inducedapoptosiswaspartially,but
6、notcompletely,blockedbyPPARγantagonist(GW9662),andsuppressionofPPARγexpressionbysiRNAalsoinhibitedPGC-1α-inducedapoptosisinHo-8910cells.ThesedatasuggestedthatPGC-1αexerteditseffectthroughaPPARγ-dependentpathway.OurfindingsindicatedthatPGC-1αwasinvolvedintheapoptoticsignaltransduc
7、tionpathwaysanddownregulationofPGC-1αmaybeakeypointinpromotingepithelialovariancancergrowthandprogression.Keywords:PGC-1α,humanepithelialovariancancer,apoptosis,microarray,PPARγCellResearch(2007)17:363-373.doi:10.1038/cr.2007.11;publishedonline20March2007IntroductionPGC-1αisamult
8、iple-functiontranscriptioncoactiva-torth