Expression of a Mutant p53 Results in an Age-Related Demographic Shift in Spontaneous Lung Tumor Formation in Transgenic Mice 英文参考文献.docVIP

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Expression of a Mutant p53 Results in an Age-Related Demographic Shift in Spontaneous Lung Tumor Formation in Transgenic Mice 英文参考文献.doc

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Expression of a Mutant p53 Results in an Age-Related Demographic Shift in Spontaneous Lung Tumor Formation in Transgenic Mice 英文参考文献

ExpressionofaMutantp53ResultsinanAge-Related DemographicShiftinSpontaneousLungTumor FormationinTransgenicMice WenruiDuan1,2*,LiGao1,2,XinWu1,2,ErinnM.Hade1,3,Jian-XinGao1,4,HaimingDing1,5,SanfordH. Barsky1,4,GregoryA.Otterson1,2,MiguelA.Villalona-Calero1,2,6 * 1ComprehensiveCancerCenter,TheOhioStateUniversityCollegeofMedicineandPublicHealth,Columbus,Ohio,UnitedStatesofAmerica,2DepartmentofInternal Medicine, The Ohio State University College of Medicine and Public Health, Columbus, Ohio, United States of America, 3The Center for Biostatistics, The Ohio State UniversityCollegeofMedicineandPublicHealth,Columbus,Ohio,UnitedStatesofAmerica,4DepartmentofPathology,TheOhioStateUniversityCollegeofMedicine andPublicHealth,Columbus,Ohio,UnitedStatesofAmerica,5DepartmentofRadiology,TheOhioStateUniversityCollegeofMedicineandPublicHealth,Columbus, Ohio, United States of America, 6Department of Pharmacology, The Ohio State University College of Medicine and Public Health, Columbus, Ohio, United States of America Abstract Background:MutationsintheP53geneareamongthemostcommongeneticabnormalitiesinhumanlungcancer.Codon 273inthesequence-specificDNAbindingdomainisoneofthemostfrequentlymutatedsites. Methodology:Toinvestigatetheroleofmutantp53inlungtumorigenesis, alungspecificp53(273H)transgenicmouse modelwasdeveloped.Ratesoflungcancerformationinthetransgenicanimalsandtheirlittermateswereevaluatedby necropsystudiesperformedinprogressiveagecohortsrangingfrom4to24months.Inordertoestablishtheinfluenceof other common genetic abnormalities in lung tumor formation in the animals, K-Ras gene mutation and p16INK4a (p16) promotermethylationwereevaluatedinatotalof281transgenicmiceand189non-transgeniclittermates. PrincipalFindings:Attheageextremesof4–12and22–24monthsnodifferenceswereobserved,withverylowprevalence oftumorsinanimalsyoungerthan12months,andarelativelyhighprevalenceatage22monthsorolder.However,the transgenicmicehadasignificanthigherlungtumorratethantheirnon-transgeniccounterparts