标题：E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway
作者：Dong, Ling-ling; Liu, Lian; Ma, Chun-hong; Li, Ji-sheng; Du, Chao; Xu, Shan; Han, Li-hui; Li, Li; Wang, Xiu-wen
作者机构：[Dong, Ling-ling; Liu, Lian; Li, Ji-sheng; Xu, Shan; Li, Li; Wang, Xiu-wen] Shandong Univ, Dept Chemotherapy, Ctr Canc, Qilu Hosp, Jinan 250012, Peopl 更多
通讯作者地址：[Liu, L]Shandong Univ, Dept Chemotherapy, Ctr Canc, Qilu Hosp, Jinan 250012, Peoples R China.
来源：ACTA PHARMACOLOGICA SINICA
关键词：ovarian cancer; E-cadherin; proliferation; mitogen-activated protein; kinase kinase (MEK); extracellular signal-related kinase (ERK); RNA; interference
摘要：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-cadherin-mediated 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 (50 mu mol/L), but not by the PI3K inhibitor wortmannin (1 mu mol/L) or PKA inhibitor H89 (10 mu mol/L).; Conclusion: E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.