bmi1基因在肺腺癌干细胞样细胞自我更新 增殖中作用的在体分析word格式论文.docxVIP

Bmi1RegulatesSelf-RenewalandTumorigenicityof CancerStemCellsinNon-SmallCellLungCancerAbstractBackgroundNon-smallcelllungcancer(NSCLC)istheleadingcauseofcancerdeathworldwidebecauseofitshighincidenceandmortalityrate.Recurrencehappensfrequentlyafterchemotherapeutictreatment.Accordingtothecancerstemcellhypothesis,asmallpopulationofcellswithintumorspossessesstem-likeproperties,andisresponsiblefortheinitiationandprogressionoftumors,butalsomaybethesourceoftumorrelapse.Inrecentyears,substantialexperimentalevidencehasbeengeneratedinsupportoftheexistenceof lungcancerstemcells(LCSCs).Stem-likecellsinlungtissuewerefirstisolatedfromnormalmouselungusingstem-cellsurfacemakers,Sca-1+/CD34+,andweretermedBASCs.Subsequently,CD133+cells,whichpossessself-renewalcapacityandcanrecapitulatelungtumorsinimmuno-deficientmice,wereidentifiedinhumanlungcancersamples.Refined investigationintothemechanismsrequiredforNSCLCtumorigenesisandchemoresistancemay leadto an improved survival rate for lung cancer patients.LCSCshavebeenenrichedbythreedifferentmethods,includingsortingforCD133+cell,selectingforside-population(SP)cellsthateffluxHoechstdyes,orisolatingcellularclusterswhichresembleself-replicatingcells(“tumorspheres”)fromsuspensioncultures.However,thesemethodspurifybothLCSCsandsomeearlyprecursorcells.LCSCsarebelievedtoberesistanttochemotherapy,inpart,duetoover-expressionofanATP-bindingcassette half-transporter,ABCG2, whichpumps drugsoutof the cellsand providesaselective survivaladvantage.Thus,CSCs arerenderedresistantto drugtreatment,includingchemotherapeuticdrugs,andABCG2mightserveasamarkerforstemcellsfromvarioussources.SinceLCSCsarerelativelyresistanttochemotherapy,weattemptedtoenrichLCSCsbyconsecutivepassagingofaNSCLCcellline,A549,inmicetreatedwithPaclitaxel.Wealsoinvestigatedthemechanismsregulatetheself-renewalandtumorigenicityofLCSCs.Bmi1isamemberofthePolycombgroup(PcG)genes,whicharetranscriptionalrepressorsthat play essentialroles in themaintenanceof appropriate gene expressionduringde