title: E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.
authors.affiliation: Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Ji'nan, China.
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Dong
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.forename: Chun-hong
authors.initials: CH
authors.lastname: Ma
authors.forename: Ji-sheng
authors.initials: JS
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Du
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.forename: Li-hui
authors.initials: LH
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xiu-wen
authors.initials: XW
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D015820:Cadherins