Extracellular Matrix Dynamics in Hepatocarcinogenesis a Comparative Proteomics Study of PDGFC Transgenic and Pten Null Mouse Models 英文参考文献.docVIP

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Extracellular Matrix Dynamics in Hepatocarcinogenesis a Comparative Proteomics Study of PDGFC Transgenic and Pten Null Mouse Models 英文参考文献.doc

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Extracellular Matrix Dynamics in Hepatocarcinogenesis a Comparative Proteomics Study of PDGFC Transgenic and Pten Null Mouse Models 英文参考文献

ExtracellularMatrixDynamicsinHepatocarcinogenesis:a ComparativeProteomicsStudyofPDGFCTransgenicand PtenNullMouseModels KeaneK.Y.Lai1.¤,SufenShang1.,NehaLohia1,GarrettC.Booth1,DerekJ.Masse1,NelsonFausto2, JeanS.Campbell2,LauraBeretta1* 1MolecularDiagnosticsProgram,PublicHealthSciencesDivision,FredHutchinsonCancerResearchCenter,Seattle,Washington,UnitedStatesofAmerica,2Department ofPathology,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica Abstract Wearereportingqualitativeandquantitativechangesoftheextracellularmatrix(ECM)andassociatedreceptorproteomes, occurringduringthetransitionfromliverfibrosisandsteatohepatitistohepatocellularcarcinoma(HCC).Wecomparedtwo mouse models relevant to human HCC: PDGFC transgenic (Tg) and Pten null mice, models of disease progression from fibrosis and steatohepatitis to HCC. Using mass spectrometry, we identified in the liver of both models proteins for 26 collagen-encodinggenes,providingthefirstevidenceofexpressionattheproteinlevelfor16collagens.Wealsoidentified post-transcriptional protein variants for six collagens and lysine hydroxylation modifications for 14 collagens. Tumor- associatedcollagenproteomesweresimilarinbothmodelswithincreasedexpressionofcollagenstypeIV,VI,VII,X,XIV,XV, XVI,andXVIII.SplicevariantsforCol4a2,Col6a2,Col6a3wereco-upregulatedwhileonlytheshortformofCol18a1increased inthetumors.Wealsoidentifiedtumorspecificincreasesofnidogen1,decorin,perlecan,andofsixlamininsubunits.The changesinthesenon-collagenousECMproteinsweresimilarinbothmodelswiththeexceptionoflamininb3,detected specifically in the Pten null tumors. Pdgfa and Pdgfc mRNA expression was increased in the Pten null liver, a possible mechanismforthesimilarityinECMcompositionobservedinthetumorsofbothmodels.Incontrastandbesidesthestrong up-regulationofintegrina5proteinobservedinthelivertumorsofbothmodels,theexpressionofthesixotherintegrins identifiedwasspecifictoeachmodel,withintegrinsa2b,a3,a6,andb1up-regulatedinPtennulltumorsandintegrinsa8 a