E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway
E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway
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E-cadherin通过激活MEK/ERK通路促进人卵巢癌细胞体外增殖
DOI：
10.1038/aps.2012.30
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发表时间：
2012-06-01
影响因子：
8.2
通讯作者：
Wang, Xiu-wen
中科院分区：
文献类型：
--
作者：
Dong, Ling-ling;Liu, Lian;Wang, Xiu-wen
目的：E-cadherin在大多数卵巢癌中异常高表达。本研究旨在探讨E-cadherin在卵巢癌发生、发展中的作用。通过RNA干扰（RNA interference，RNAi）技术敲除SKOV-3细胞中的E-钙粘蛋白基因CDH 1，并通过CCK-8和集落形成实验观察其生物学行为的变化。应用E-cadherin介导的钙依赖性细胞间粘附研究E-cadherin对SKOV-3细胞增殖和存活的影响。结果：CDH 1-siRNA转染SKOV-3细胞24-96 h后，SKOV-3细胞的生长和增殖明显受到抑制，细胞外信号相关激酶（ERK）、磷酸化ERK（P-ERK）的表达水平明显升高。E-cadherin介导的SKOV-3细胞的钙依赖性细胞-细胞粘附导致P-ERK的快速增加，但不改变ERK蛋白的表达。用MEK 1特异性抑制剂PD 98059（50 μmol/L）预处理卵巢上皮癌细胞，可阻断ERK的磷酸化，而用PI 3 K抑制剂wortmannin（1 μmol/L）或PKA抑制剂H89（10 μmol/L）预处理卵巢上皮癌细胞，则不能阻断ERK的磷酸化。
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 Ca 2+-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 μmol/L), but not by the PI3K inhibitor wortmannin (1 μmol/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.