Abstract
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 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.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (grant No 30772329 and 81172487), China Postdoctoral Science Foundation (grant No 20090450153), Grant for Postdoctoral Researchers with Creative Projects of Shandong Province, China (No 200801009) and Natural Science Foundation of Shandong Province, China (grant No ZR2009CM004).
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Dong, Ll., Liu, L., Ma, Ch. et al. E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway. Acta Pharmacol Sin 33, 817–822 (2012). https://doi.org/10.1038/aps.2012.30
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DOI: https://doi.org/10.1038/aps.2012.30
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