Down-Regulation of Yes Associated Protein 1 Expression Reduces Cell Proliferation and Clonogenicity of Pancreatic Cancer Cells 英文参考文献.docVIP

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Down-Regulation of Yes Associated Protein 1 Expression Reduces Cell Proliferation and Clonogenicity of Pancreatic Cancer Cells 英文参考文献.doc

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Down-Regulation of Yes Associated Protein 1 Expression Reduces Cell Proliferation and Clonogenicity of Pancreatic Cancer Cells 英文参考文献

Down-RegulationofYesAssociatedProtein1Expression ReducesCellProliferationandClonogenicityof PancreaticCancerCells CarolineH.Diep1,KellyM.Zucker1,GalenHostetter2,AprillWatanabe2,ChengchengHu3,RubenM. Munoz1,DanielD.VonHoff1,HaiyongHan1* 1Clinical Translational Division, Translational Genomics Research Institute, Scottsdale, Arizona, United States of America, 2Integrated Cancer Genomics Division, TranslationalGenomicsResearchInstitute,Scottsdale,Arizona,UnitedStatesofAmerica,3EpidemiologyandBiostatisticsDivision,CollegeofPublicHealth,Universityof Arizona,Tucson,Arizona,UnitedStatesofAmerica Abstract Background:TheHippopathwayregulatesorgansizebyinhibitingcellproliferationandpromotingcellapoptosisuponits activation.TheYesAssociatedProtein1(YAP1)isanucleareffectoroftheHippopathwaythatpromotescellgrowthasa transcriptionco-activator.Inhumancancer,theYAP1genewasreportedasamplifiedandover-expressedinseveraltumor types. Methods:ImmunohistochemicalstainingofYAP1proteinwasusedtoassesstheexpressionofYAP1inpancreatictumor tissues.siRNAoligonucleotideswereusedtoknockdowntheexpressionofYAP1andtheireffectsonpancreaticcancercells wereinvestigatedusingcellproliferation,apoptosis,andanchorage-independentgrowthassays.TheWilcoxonsigned-rank, Pearsoncorrelationcoefficient,Kendall’sTau,Spearman’sRho,andanindependenttwo-samplet(two-tailed)testwereused todeterminethestatisticalsignificanceofthedata. Results: Immunohistochemistry studies in pancreatic tumor tissues revealed YAP1 staining intensities were moderate to stronginthenucleusandcytoplasmofthetumorcells,whereastheadjacentnormalepithelialshowednegativetoweak staining.Inculturedcells,YAP1expressionandlocalizationwasmodulatedbycelldensity.YAP1totalproteinexpression increasedinthenuclearfractionsinBxPC-3andPANC-1,whileitdeclinedinHPDE6ascelldensityincreased.Additionally, treatment of pancreatic cancer cell lines, BxPC-3 and PANC-1, with YAP1-targeting siRNA oligonucleotides significantly reducedtheirproliferationinvitro.Furthermore,tre