title: Oestrogen receptor α mediates 17β-estradiol enhancement of ovarian cancer cell motility through up-regulation of survivin expression.
abstract: OBJECTIVE
  To determine the role of oestrogen receptor α (ERα) in the regulation of survivin expression by 17β-estradiol (E(2)) in ovarian cancer cells and to evaluate the mechanism of E(2) action on ovarian cancer cell migration.
  
  
  METHODS
  We performed RT-PCR and Western blot analysis to assess the expression of ERα in the ovarian cancer cell lines NIH:OVCAR-3 and SKOV-3. Full-length ERα cDNA was reintroduced into SKOV-3 cells through stable transfection. After treatment with E(2), with or without pre-incubation of anti-oestrogen compound ICI 182780, RT-PCR and Western blot analysis were performed to detect survivin expression at the mRNA and protein levels. RNA interference (RNAi) was used to inhibit the expression of survivin in SKOV-3 cells. Wound healing-induced migration and Matrigel invasion experiments were performed to determine the motility of ovarian cancer cells. RT-PCR and gelatin zymography were used to detect the expression and activity of MMP-9 in SKOV-3 cells.
  
  
  RESULTS
  A stably transfected clone with over-expression of ERα, SKOV-α, was isolated. Exogenous or endogenous expression of ERα in SKOV-3 or NIH:OVCAR-3 cells resulted in a significant up-regulation of survivin in the presence of E(2). Pre-treatment with ICI 182780 attenuated the up-regulation of survivin by E(2). Previous data from our laboratory showed that E(2) enhanced the motility of ovarian cancer cells. RNAi strongly inhibited survivin expression in SKOV-3 cells. Knock-down of survivin expression reduced the migration and invasion of SKOV-3 cells, which correlated with down-regulation of MMP9 mRNA expression and activity.
  
  
  CONCLUSIONS
  ERα may be responsible for the up-regulation of survivin after E(2) treatment in ovarian cancer cells. The mechanism of oestrogen-promoted ovarian cancer metastasis may due to the up-regulation of survivin conducted through the ERα signalling pathway.
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital at Fudan University, 419 Fang Xie Road, Shanghai, 200011, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Hua
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Yin-Hua
authors.initials: YH
authors.lastname: Yu
authors.forename: You-Ji
authors.initials: YJ
authors.lastname: Feng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D018076:DNA, Complementary; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D061986:MCF-7 Cells; D051379:Mice; D041681:NIH 3T3 Cells; D010051:Ovarian Neoplasms / Q000378:metabolism*; D000077022:Survivin; D014162:Transfection; D015854:Up-Regulation
chemical_list: C107489:BIRC5 protein, human; D018076:DNA, Complementary; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D004958:Estradiol