Epithelial Tissues Have Varying Degrees of Susceptibility to KrasG12D-Initiated Tumorigenesis in a Mouse Model 英文参考文献.docVIP

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Epithelial Tissues Have Varying Degrees of Susceptibility to KrasG12D-Initiated Tumorigenesis in a Mouse Model 英文参考文献.doc

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Epithelial Tissues Have Varying Degrees of Susceptibility to KrasG12D-Initiated Tumorigenesis in a Mouse Model 英文参考文献

EpithelialTissuesHaveVaryingDegreesofSusceptibility toKrasG12D-InitiatedTumorigenesisinaMouseModel KevinC.Ray1,KaylaM.Bell1,JingboYan2,GuoqiangGu2,ChristineH.Chung3,M.KayWashington4, AnnaL.Means1,2 * 1Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America, 2Department of Cell and Developmental Biology, VanderbiltUniversityMedicalCenter,Nashville,Tennessee,UnitedStatesofAmerica,3DepartmentofOncology,JohnsHopkinsUniversitySchoolofMedicine,Baltimore, Maryland,UnitedStatesofAmerica,4DepartmentofPathology,VanderbiltUniversityMedicalCenter,Nashville,Tennessee,UnitedStatesofAmerica Abstract ActivatingmutationsintheKrasgenearecommonlyfoundinsomebutnotallepithelialcancers.Inordertounderstandthe susceptibility of different epithelial tissues toKras-induced tumorigenesis, weintroduced one of themost common Kras mutations, KrasG12D, broadly in epithelial tissues. We used a mouse model in which the G12D mutation is placed in the endogenousKraslocuscontrolledbyinducible,Cre-mediatedrecombinationintissuesexpressingcytokeratin19including theoralcavity,GItract,lungs,andductsoftheliver,kidney,andthepancreas.IntroductionoftheKrasG12Dmutationinadult mousetissuesledtoneoplasticchangesinsomebutnotallofthesetissues.Notably,manyhyperplasias,metaplasiasand adenomaswereobservedintheoralcavity,stomach,colonandlungs,suggestingthatexposuretoproductsoftheoutside environmentpromotesKrasG12D-initiatedtumorigenesis. However,environmentalexposuredidnotconsistentlycorrelate withtumorformation,suchasinthesmallintestine,suggestingthattherearealsointrinsicdifferencesinsusceptibilityto Kras activation. The pancreas developed small numbers of mucinous metaplasias with characteristics of early stage pancreaticintraepithelialneoplasms(PanINs),supportingthehypothesisthatpancreaticductshavethepotentialtogive risepancreaticcancer. Citation:RayKC,BellKM,YanJ,GuG,ChungCH,etal.(2011)EpithelialTissuesHaveVaryingDegreesofSusceptibilitytoKrasG12D-InitiatedTumor