Genetic Deletion of the Desmosomal Component Desmoplakin Promotes Tumor Microinvasion in a Mouse Model of Pancreatic Neuroendocrine Carcinogenesis 英文参考文献.docVIP

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Genetic Deletion of the Desmosomal Component Desmoplakin Promotes Tumor Microinvasion in a Mouse Model of Pancreatic Neuroendocrine Carcinogenesis 英文参考文献.doc

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Genetic Deletion of the Desmosomal Component Desmoplakin Promotes Tumor Microinvasion in a Mouse Model of Pancreatic Neuroendocrine Carcinogenesis 英文参考文献

GeneticDeletionoftheDesmosomalComponent DesmoplakinPromotesTumorMicroinvasioninaMouse ModelofPancreaticNeuroendocrineCarcinogenesis MatthewG.H.Chun1,2,DouglasHanahan1,3 * 1Department of Biochemistry and Biophysics, Helen Diller Family Comprehensive Cancer Center, and Diabetes Center, University of California San Francisco, San Francisco,California,UnitedStatesofAmerica,2PrograminBiologicalSciences,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica, 3SwissInstituteforExperimentalCancerResearch(ISREC),SwissFederalInstituteofTechnologyLausanne(EPFL),Lausanne,Switzerland Abstract We used the RIP1-Tag2 (RT2) mouse model of islet cell carcinogenesis to profile the transcriptome of pancreatic neuroendocrine tumors (PNET) that were either non-invasive or highly invasive, seeking to identify pro- and anti- invasive molecules. Expression of multiple components of desmosomes, structures that help maintain cellular adhesion, wassignificantly reduced ininvasive carcinomas. Genetic deletion ofoneofthesedesmosomal components, desmoplakin, resulted in increased local tumor invasion without affecting tumor growth parameters in RT2 PNETs. Expression of cadherin 1, a component of the adherens junction adhesion complex, was maintained in these tumors despite thegenetic deletion ofdesmoplakin.Ourresults demonstrate thatlossofdesmoplakin expression andresultant disruption of desmosomal adhesion can promote increased local tumor invasion independent of adherens junction status. Citation:Chun MGH,HanahanD(2010)GeneticDeletion oftheDesmosomalComponent DesmoplakinPromotesTumorMicroinvasioninaMouseModelof PancreaticNeuroendocrineCarcinogenesis.PLoSGenet6(9):e1001120.doi:10.1371/journal.pgen.1001120 Editor:BruceE.Clurman,FredHutchinsonCancerResearchCenter,UnitedStatesofAmerica ReceivedApril13,2010;AcceptedAugust12,2010;PublishedSeptember16,2010 Copyright: ? 2010 Chun, Hanahan. This is an open-access article distributed under the terms of the Creative Com