《Histone Demethylase RBP2 Promotes Lung Tumorigenesisand Cancer Metastasis組蛋白脫甲基酶rbp2促進肺腫瘤 與腫瘤轉(zhuǎn)移》由會員上傳分享，免費在線閱讀，更多相關(guān)內(nèi)容在學(xué)術(shù)論文-天天文庫。

1、PublishedOnlineFirstMay30,2013;DOI:10.1158/0008-5472.CAN-12-3165CancerMolecularandCellularPathobiologyResearchHistoneDemethylaseRBP2PromotesLungTumorigenesisandCancerMetastasis1,411221Yu-ChingTeng,Cheng-FengLee,Ying-ShiuanLi,Yi-RenChen,Pei-WenHsiao,Meng-YuChan,771518Feng-MaoLin,Hsien-DaHu

2、ang,Yen-TingChen,Yung-MingJeng,Chih-HungHsu,QinYan,1,3,4,61,4Ming-DawTsai,andLi-JungJuanAbstractTheretinoblastomabindingproteinRBP2(KDM5A)isahistonedemethylasethatpromotesgastriccancercellgrowthandisenrichedindrug-resistantlungcancercells.Intumor-pronemicelackingthetumorsuppressorgeneRBor

3、MEN1,geneticablationofRBP2cansuppresstumorinitiation,butthepathogenicbreadthandmechanisticaspectsofthiseffectrelativetohumantumorshavenotbeende?ned.Here,weapproachedthisquestioninthecontextoflungcancer.RBP2wasoverexpressedinhumanlungcancertissueswhereitsdepletionimpairedcellproliferation,

4、motility,migration,invasion,andmetastasis.RBP2oncogenicityreliedonitsdemethylaseandDNA-bindingactivities.RBP2upregulatedexpressionofcyclinsD1andE1whilesuppressingtheexpressionofcyclin-dependentkinaseinhibitorp27(CDKN1B),eachcontributingtoRBP2-mediatedcellproliferation.Expressionmicroarray

5、analysesrevealedthatRBP2promotedexpressionofintegrin-b1(ITGB1),whichisimplicatedinlungcancermetastasis.MechanisticinvestigationsestablishedthatRBP2bounddirectlytothep27,cyclinD1,andITGB1promotersandthatexogenousexpressionofcyclinD1,cyclinE1,orITGB1wassuf?cienttorescueproliferationormigrat

6、ion/invasion,respectively.Takentogether,ourresultsestablishanoncogenicroleforRBP2inlungtumorigenesisandprogressionanduncovernovelRBP2targetsmediatingthisrole.CancerRes;73(15);4711–21.ó2013AACR.IntroductioningonitsJmjCdomain(8,9).Therefore,RBP2isalsocalledKDM5AorJARID1A.ThehumanJARID1prote

7、infamilycon-Retinoblastomabindingprotein-2(RBP2)wasoriginallysistsoffourmembersincludingRBP2/JARID1A,PLU1/JAR-identi?edasaretinoblastomaprotein(Rb)-bindingpartnerID1B,SMCX/JARID1C,andSMCY/JARID1D(10).Thesefour(1).Subsequently,itwasshowntoparticipateintranscriptionpr