Down-Regulation of GEP100 Causes Increase in E-Cadherin Levels and Inhibits Pancreatic Cancer Cell Invasion 英文参考文献.docVIP

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Down-Regulation of GEP100 Causes Increase in E-Cadherin Levels and Inhibits Pancreatic Cancer Cell Invasion 英文参考文献.doc

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Down-Regulation of GEP100 Causes Increase in E-Cadherin Levels and Inhibits Pancreatic Cancer Cell Invasion 英文参考文献

Down-RegulationofGEP100CausesIncreaseinE- CadherinLevelsandInhibitsPancreaticCancerCell Invasion Chuan-gaoXie1,Shu-meiWei2*,Jia-minChen1,Xuan-fuXu3,Jian-tingCai1*,Qin-yuChen1,Li-taoJia1 1Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou City, Zhejiang Province, China, 2Department of Pathology, Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou City, Zhejiang Province, China, 3Department of Gastroenterology, Tenth HospitalofTongjiUniversity,ShanghaiCity,China Abstract Aims:Invasionandmetastasisaremajorreasonsforpancreaticcancerdeathandidentifyingsignalingmoleculesthatare specificallyusedintumorinvasionisofgreatsignificance.ThepurposeofthisstudywastoelucidatetheroleofGEP100in pancreaticcancercellinvasionandmetastasisandthecorrespondingmolecularmechanism. Methods: Stable cell lines with GEP100 knocked-down were established by transfecting GEP100 shRNA vector into PaTu8988cellsandselectedbypuromycin.qRT-PCRandWesternblotwereperformedtodetectgeneexpression.Matrigel- invasionassaywasusedtodetectcancercellinvasioninvitro.Livermetastasisinvivowasdeterminedbysplenicinjectionof indicatedcelllinesfollowedbyspleenresection.Immunofluorescencestudywasusedtodetecttheintracellularlocalization ofE-cadherin. Results: WefoundthattheexpressionlevelofGEP100proteinwascloselyrelatedtotheinvasiveabilityofapanelof6 differenthumanpancreaticcancercelllines.Down-regulationofGEP100inPaTu8988cellssignificantlydecreasedinvasive activitybyMatrigel invasionassay,withoutaffecting migration,invasionandviability.Theinhibitedinvasive activitywas rescuedbyover-expressionofGEP100cDNA.Invivostudyshowedthatlivermetastasiswassignificantlydecreasedinthe PaTu8988 cells with GEP100 stably knocked-down. In addition, an epithelial-like morphological change, mimicking amesenchymaltoepithelialtransition(MET)wasinducedbyGEP100down-regulation.TheexpressionofE-cadherinprotein wasincreased2–3foldsaccompaniedbyitsredistrib