Gastrointestinal Hyperplasia with Altered Expression of DNA Polymerase β 英文参考文献.docVIP

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Gastrointestinal Hyperplasia with Altered Expression of DNA Polymerase β 英文参考文献.doc

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Gastrointestinal Hyperplasia with Altered Expression of DNA Polymerase β 英文参考文献

GastrointestinalHyperplasiawithAlteredExpressionof DNAPolymeraseb KatsuhikoYoshizawa4,5,ElenaJelezcova1,AshleyR.Brown1,JulieF.Foley4,AbrahamNyska4 ,Xiangli Cui6,LorneJ.Hofseth6,RobertM.Maronpot4,SamuelH.Wilson3,AntoniaR.Sepulveda7,RobertW. Sobol1,2 * 1Department of Pharmacology Chemical Biology, University of Pittsburgh School of Medicine University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh,Pennsylvania,UnitedStatesofAmerica,2DepartmentofHumanGenetics,UniversityofPittsburghGraduateSchoolofPublicHealth,Pittsburgh,Pennsylvania, UnitedStatesofAmerica,3LaboratoryofStructuralBiology,NationalInstituteofEnvironmentalHealthSciences,ResearchTrianglePark,NorthCarolina,UnitedStatesof America,4CellularandMolecularPathologyBranch,NationalInstituteofEnvironmentalHealthSciences,ResearchTrianglePark,NorthCarolina,UnitedStatesofAmerica, 5DepartmentofPathologyII,KansaiMedicalUniversity,Moriguchi,Osaka,Japan,6DepartmentofPharmaceuticalandBiomedicalSciences,SouthCarolinaCollegeof Pharmacy, University of South Carolina, Columbia, South Carolina, United States of America, 7Department of Pathology and Laboratory Medicine, Hospital of the UniversityofPennsylvania,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract Background: Altered expression of DNA polymerase b (Pol b) has been documented in a large percentage of human tumors.However,tumorprevalenceorpredispositionresultingfromPolbover-expressionhasnotyetbeenevaluatedina mousemodel. Methodology/PrincipalFindings:Wehaverecentlydevelopedanoveltransgenicmousemodelthatover-expressesPolb. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner’sglandandmucosalhyperplasiaintheduodenum.Inaddition,osteogenictumorsinmicetails,suchasosteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol b over- expression.ThesefindingspromptedanevaluationofhumangastrointestinaltumorswithregardtoPolbex