Aim:E-cadherin is unusually highly expressed in most ovarian cancers.This study was designed to investigate the roles of E-cadherin in the carcinogenesis and progression of ovarian cancers.Methods:Human ovarian adenocarcinoma cell line SKOV-3 was examined.E-cadherin gene CDH1 in SKOV-3 cells was knocked down via RNA interference (RNAi),and the resultant variation of biological behavior was observed using CCK-8 and colony formation experiment.E-cadherin-mediated Ca2+-dependent cell-cell adhesion was used to study the mechanisms underlying the effects of E-cadherin on the proliferation and survival of SKOV-3 cells.The expression levels of E-cadherin,extracellular signal-related kinase (ERK),phosphorylated ERK (P-ERK) were measured using Western blot assays.Results:Transfection with CDH1-siRNA for 24-96 h significantly suppressed the growth and proliferation of SKOV-3 cells.E-cadhednmediated calcium-dependent cell-cell adhesion of SKOV-3 cells resulted in a rapid increase of P-ERK,but did not modify the expression of ERK protein.The phosphorylation of ERK in the cells was blocked by pretreatment with the MEK1 specific inhibitor PD98059 (50μmol/L),but not bythe PI3K inhibitor wortmannin (1μmol/L) or PKA inhibitor H89 (10 μmol/L).Conclusion:E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.
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