Expression of the Bcl-2 Protein BAD Promotes Prostate Cancer Growth 英文参考文献.docVIP

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Expression of the Bcl-2 Protein BAD Promotes Prostate Cancer Growth 英文参考文献.doc

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Expression of the Bcl-2 Protein BAD Promotes Prostate Cancer Growth 英文参考文献

ExpressionoftheBcl-2ProteinBADPromotesProstate CancerGrowth AdrienneJ.Smith1,YelenaKarpova1,RalphD’Agostino,Jr.2,MarkWillingham2,3,GeorgeKulik1,2 * 1DepartmentofCancerBiology,WakeForestUniversitySchoolofMedicine,Winston-Salem,NorthCarolina,UnitedStatesofAmerica,2ComprehensiveCancerCenter, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America, 3Department of Pathology, Wake Forest University School of Medicine,Winston-Salem,NorthCarolina,UnitedStatesofAmerica Abstract BAD, a pro-apoptotic protein of the Bcl-2 family, has recently been identified as an integrator of several anti-apoptotic signalingpathwaysinprostatecancercells.Thus,activationofEGFR,GPCRsorPI3KpathwayleadstoBADphosphorylation and inhibition of apoptosis. Increased levels of BAD in prostate carcinomas have also been reported. It appears contradictory that instead of limiting expression of pro-apoptotic protein, prostate cancer cells choose to increase BAD levelswhilekeepingitundertightphosphorylationcontrol.AnalysisoftheeffectofBADonprostatecancerxenograftshas shown that increased BAD expression enhances tumor growth, while knockdown of BAD expression by shRNA inhibits tumorgrowth.TissuecultureexperimentsdemonstratedthatincreasedBADexpressionstimulatesproliferationofprostate cancercells.TheseresultssuggestthatincreasedexpressionofBADprovidesaproliferativeadvantagetoprostatetumors, whileBADdephosphorylationincreasessensitivityofprostatecancercellstoapoptosis.Combinationofproliferativeand apoptotic properties prompts prostate cancer cells to be ‘‘addicted’’ to increased levels of phosphorylated BAD. Thus, kinasesthatphosphorylateBADareplausibletherapeutictargets;whilemonitoringBADphosphorylationcouldbeusedto predicttumorresponsetotreatments. Citation:SmithAJ,KarpovaY,D’AgostinoRJr,WillinghamM,KulikG(2009)ExpressionoftheBcl-2ProteinBADPromotesProstateCancerGrowth.PLoSONE4(7): e6224.doi:10.1371/journal.pone.0006224 Editor:SyedA.Aziz,HealthCanada,Canada Received