Down-Regulation of CDH1 Is Associated with Expression of SNAI1 in Colorectal Adenomas 英文参考文献.docVIP

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Down-Regulation of CDH1 Is Associated with Expression of SNAI1 in Colorectal Adenomas 英文参考文献.doc

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Down-Regulation of CDH1 Is Associated with Expression of SNAI1 in Colorectal Adenomas 英文参考文献

Down-RegulationofCDH1IsAssociatedwithExpression ofSNAI1inColorectalAdenomas FerideKroepil1.,GeorgFluegen1.,ZaurbekTotikov1,StephanE.Baldus2,ChristianVay1, MatthiasSchauer1,StefanA.Topp1,JanSchulteamEsch1,WolframT.Knoefel1,NikolasH.Stoecklein1* 1DepartmentofGeneral-,Visceral-andPediatricSurgery,UniversityHospitalDu¨sseldorf,Du¨sseldorf,Germany,2InstituteforPathology,UniversityHospitalDu¨sseldorf, Du¨sseldorf,Germany Abstract Introduction: Down-regulation of E-cadherin (CDH1) and epithelial-mesenchymal transition (EMT) are considered critical eventsforinvasionandmetastasisofcolorectalcarcinoma.HerewetestedwhethertheimportantregulatorsofE-cadherin expressionSNAI1andTWIST1arealreadydetectableinhumancolorectaladenomas. Methods: RNA was extracted from a set of randomly selected formalin-fixed and paraffin-embedded (FFPE) colorectal adenomas(n=41)andnormalcolonmucosa(n=10).SubsequentlymRNAexpressionofCDH1,CDH2,SNAI1andTWIST1 was analysed by quantitative RT-PCR analysis. CDH1 as well as SNAI1 protein expression were assessed by immunohistochemistry(IHC). Results:SNAI1mRNAwasexpressedin78%(n=32/41),TWIST1mRNAin41%(n=17/41)andCDH2mRNAin41%(n=17/ 41)ofthecolorectaladenomatissue,whilenormalcolonmucosawasnegativeforthesetranscriptionfactors.Wefounda significantcorrelationbetweenreducedCDH1andthepresenceofSNAI1mRNAexpressionandforcombinedSNAI1and TWIST1mRNAexpression,respectively.AcorrelationbetweenCDH2mRNAexpressionandreducedCDH1expressionwas notobserved.WeconfirmedtherelationshipbetweenSNAI1expressionandreducedE-cadherinexpressionontheprotein levelviaIHC. Conclusion:OurdatashowthatSNAI1andTwist1arealreadyexpressedinbenignprecursorlesionsofcolorectalcancer andthatSNAI1expressionwassignificantlycorrelatedwithlowerexpressionofCDH1.Whetherthesefindingsreflecttrue EMTand/orareasignofamoreaggressivebiologyneedtobeinvestigatedinfurtherstudies. Citation: Kroepil F, Fluegen G, Totikov Z, Baldus SE, Vay C, et al. (2012) Down-Regulation of CDH1 Is Associated with Expression of SNAI1