Breast Cancer Stem Cell-Like Cells Are More Sensitive to Ionizing Radiation than Non-Stem Cells Role of ATM 英文参考文献.docVIP

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Breast Cancer Stem Cell-Like Cells Are More Sensitive to Ionizing Radiation than Non-Stem Cells Role of ATM 英文参考文献.doc

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Breast Cancer Stem Cell-Like Cells Are More Sensitive to Ionizing Radiation than Non-Stem Cells Role of ATM 英文参考文献

BreastCancerStemCell-LikeCellsAreMoreSensitiveto IonizingRadiationthanNon-StemCells:RoleofATM Seog-YoungKim1,JuongG.Rhee2,XinxinSong1,EdwardV.Prochownik3,4,DouglasR.Spitz5, YongJ.Lee1* 1DepartmentofSurgery,SchoolofMedicine,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,2TheRadiationOncologyResearchLaboratory, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America, 3Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 4Department of Molecular Genetics and Biochemistry, School of Medicine, UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,5FreeRadicalandRadiationBiologyProgram,DepartmentofRadiationOncology,Holden ComprehensiveCancerCenter,TheUniversityofIowa,IowaCity,Iowa,UnitedStatesofAmerica Abstract Therearecontradictoryobservationsaboutthedifferentradiosensitivitiesofcancerstemcellsandcancernon-stemcells.To resolvethesecontradictoryobservations,westudiedradiosensitivitiesbyemployingbreastcancerstemcell(CSC)-likeMDA- MB231andMDA-MB453cellsaswellastheircorrespondingnon-stemcells.CSC-likecellsproliferatewithoutdifferentiating andhavecharacteristicsoftumor-initiatingcells[1].Thesecellswereexposedtoc-rays(1.25–8.75Gy)andsurvivalcurves weredeterminedbycolonyformation.Afinalslope,D0,ofthesurvivalcurveforeachcelllinewasdeterminedtomeasure radiosensitivity.TheD0ofCSC-likeandnon-stemMDA-MB-453cellswere1.16Gyand1.55Gy,respectively.Similarresults wereobservedinMDA-MB-231cells(0.94Gyvs.1.56Gy).Afterdeterminationofradiosensitivity,weinvestigatedintrinsic cellular determinants which influence radiosensitivity including cell cycle distribution, free-radical scavengers and DNA repair. We observed that even though cell cycle status and antioxidant content may contribute to differential radiosensitivity, differential DNA repair capacity may be a greater determinant of radiosensitivity. Unlike non-stem c