Expression of Abelson Interactor 1 (Abi1) Correlates with Inflammation, KRAS Mutation and Adenomatous Change during Colonic Carcinogenesis 英文参考文献.docVIP

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Expression of Abelson Interactor 1 (Abi1) Correlates with Inflammation, KRAS Mutation and Adenomatous Change during Colonic Carcinogenesis 英文参考文献.doc

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Expression of Abelson Interactor 1 (Abi1) Correlates with Inflammation, KRAS Mutation and Adenomatous Change during Colonic Carcinogenesis 英文参考文献

ExpressionofAbelsonInteractor1(Abi1)Correlateswith Inflammation,KRASMutationandAdenomatousChange duringColonicCarcinogenesis KonradSteinestel1,2*,SilkeBru¨derlein1,JulieSteinestel3,BrunoMa¨rkl4,MichaelJ.Schwerer5, AnnetteArndt2,KlausKraft2,ChristianPro¨pper6,PeterMo¨ller1 1InstituteofPathology,UniversityofUlm,Ulm,Germany,2DepartmentofPathology,BundeswehrkrankenhausUlm,Ulm,Germany,3DepartmentofUrology,University ofUlm,Ulm,Germany,4InstituteofPathology,KlinikumAugsburg,Augsburg,Germany,5DepartmentofForensicMedicine/AircraftAccidentInvestigation,GermanAir ForceInstituteofAviationMedicine,Fu¨rstenfeldbruck,Germany,6InstituteofAnatomyandCellBiology,UniversityofUlm,Ulm,Germany Abstract Background:Abelsoninteractor1(Abi1)isanimportantregulatorofactindynamicsduringcytoskeletalreorganization.In this study, ouraim was toinvestigatetheexpression ofAbi1 in colonic mucosawith andwithoutinflammation, colonic polyps,colorectalcarcinomas(CRC)andmetastasesaswellasinCRCcelllineswithrespecttoBRAF/KRASmutationstatus andtofindoutwhetherintroductionofKRASmutationorstimulationwithTNFalphaenhancesAbi1proteinexpressionin CRCcells. Methodology/Principal Findings: We immunohistochemically analyzed Abi1 protein expression in 126 tissue specimens from95 patients andin5 colorectal carcinoma celllineswith differentmutation statusby western immunoblotting. We foundthatAbi1expressioncorrelatedpositivelywithKRAS,butnotBRAFmutationstatusintheexaminedtissuesamples. Furthermore, Abi1 is overexpressed in inflammatory mucosa, sessile serrated polyps and adenomas, tubular adenomas, invasive CRC and CRC metastasis when compared to healthy mucosa and BRAF-mutated as well as KRAS wild-type hyperplastic polyps. Abi1expression incarcinoma was independentof microsatellite stability of thetumor.Abi1 protein expressioncorrelatedwithKRAS mutationintheanalyzedCRCcelllines,andupregulation ofAbi1 couldbeinducedby TNFalphatreatmentaswellastransfectionofwild-typeCRCcellswithmutantKRAS.TheoverexpressionofAbi1c