ERK12 Signaling Plays an Important Role in Topoisomerase II Poison-Induced G2M Checkpoint Activation 英文参考文献.docVIP

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ERK12 Signaling Plays an Important Role in Topoisomerase II Poison-Induced G2M Checkpoint Activation 英文参考文献.doc

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ERK12 Signaling Plays an Important Role in Topoisomerase II Poison-Induced G2M Checkpoint Activation 英文参考文献

ERK1/2SignalingPlaysanImportantRolein TopoisomeraseIIPoison-InducedG2/MCheckpoint Activation RyanH.Kolb,PatrickM.Greer,PhuT.Cao,KennethH.Cowan,YingYan* EppleyInstituteforResearchinCancerandAlliedDiseases,UniversityofNebraskaMedicalCenter,Omaha,Nebraska,UnitedStatesofAmerica Abstract TopoIIpoisons,whichtargettopoisomeraseII(topoII)togenerateenzymemediatedDNAdamage,havebeencommonly usedforanti-cancertreatment.WhileclinicalevidencedemonstrateacapabilityoftopoIIpoisonsininducingapoptosisin cancercells,accumulatingevidencealsoshowthattopoIIpoisontreatmentfrequentlyresultsincellcyclearrestincancer cells,whichwasassociatedwithsubsequentresistancetothesetreatments.Resultsinthisreportindicatethattreatmentof MCF-7andT47DbreastcancercellswithtopoIIpoisonsresultedinanincreasedphosphorylationofextracellularsignal- regulatedkinase1and2(ERK1/2)andansubsequentinductionofG2/Mcellcyclearrest.Furthermore,inhibitionofERK1/2 activationusingspecificinhibitorsmarkedlyattenuatedthetopoIIpoison-inducedG2/MarrestanddiminishedthetopoII poison-inducedactivationofATRandChk1kinases.Moreover,decreasedexpressionofATRbyspecificshRNAdiminished topoIIpoison-inducedG2/MarrestbuthadnoeffectontopoIIpoison-inducedERK1/2activation.Incontrast,inhibitionof ERK1/2 signaling hadlittle, ifany, effect on topo II poison-induced ATMactivation. Inaddition, ATM inhibitionby either incubationofcellswithATMspecificinhibitorortransfectionofcellswithATMspecificsiRNAdidnotblocktopoIIpoison- inducedG2/Marrest.Ultimately,inhibitionofERK1/2signalinggreatlyenhancedtopoIIpoison-inducedapoptosis.These resultsimplicateacriticalroleforERK1/2signalingintheactivationofG2/McheckpointresponsefollowingtopoIIpoison treatment,whichprotectscellsfromtopoIIpoison-inducedapoptosis. Citation:KolbRH,GreerPM,CaoPT,CowanKH,YanY(2012)ERK1/2SignalingPlaysanImportantRoleinTopoisomeraseIIPoison-InducedG2/MCheckpoint Activation.PLoSONE7(11):e50281.doi:10.1371/journal.pone.0050281 Editor:MingTan,UniversityofSouthAlabama,UnitedStatesofAmerica Receiv