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1、TheProstate73:624^633(2013)InhibitorofDifferentiation1(Id1)andId3ProteinsPlayDifferentRolesinTGFbEffectsonCellProliferationandMigrationinProstateCancerCellsNicoleStrong,AnaC.Millena,LindseyWalker,JaideepChaudhary,andShafiqA.Khan*CenterforCancerResearchandTherapeuticDevelopment,
2、ClarkAtlantaUniversity,Atlanta,GeorgiaBACKGROUND.Inprostatecancercells,transforminggrowthfactorb(TGFb)inhibitspro-liferationinearlierstagesofthedisease;however,thecancercellsbecomerefractorytogrowthinhibitoryeffectsinadvancedstageswhereTGFbpromotescancerprogressionandmetastasis
3、.Inhibitorofdifferentiation(Id)familyofcloselyrelatedproteins(Id1–Id4)aredominantnegativeregulatorsandbasichelixloophelix(bHLH)transcriptionfactorsandingeneralpromoteproliferation,andinhibitdifferentiation.Inthepresentstudy,wehaveinvestigatedtheroleofId1andId3proteinsinthegrowt
4、hinhibitoryeffectsofTGFbonprostatecancercells.METHODS.TheeffectofTGFbonproliferationandId1andId3expressionwereinvesti-gatedinPZ-HPV7,DU145,andPC3cells.Id1silencingthroughsiRNAwasalsousedinDU145andPC3cellstoexamineitsroleinanti-proliferativeandmigratoryeffectsofTGFb.RESULTS.TGFb
5、increasedexpressionofId1andId3inallcelllinesfollowedbyalaterdownregulationofId1inPZ-HPV7expressionandDU145cellsbutnotinPC3cells.Id3expressionremainedelevatedinallthreecelllines.ThislossofId1proteincorrelatedwithanincreaseofCDKNIp21.Id1knockdowninbothDU145andPC3cellsresultedinde
6、creasedproliferation.However,whileTGFbcausedafurtherdecreaseinproliferationofDU145,buthadnofurthereffectsinPC3cells.KnockdownofId1orId3inhibitedTGFb1inducedmigra-tioninPC3cells.CONCLUSIONS.ThesefindingssuggestanessentialroleofId1andId3inTGFb1effectsonproliferationandmigrationin
7、prostatecancercells.Prostate73:624–633,2013.#2012WileyPeriodicals,Inc.KEYWORDS:prostatecancer;cellproliferation;migration;TGFb;inhibitorofdifferentiation(Id)INTRODUCTIONmolecularmechanismsandintracellulareffectorssurroundingthesedifferentialeffectsofTGFb1dur-Transforminggrowthf
8、actorb(TGFb),amemberofingdifferentstagesofcancerprogre
