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- Title
Oestrogen receptor α mediates 17β-estradiol enhancement of ovarian cancer cell motility through up-regulation of survivin expression.
- Authors
Zhu, Jing; Lu, Xin; Hua, Ke-Qin; Sun, Hong; Yu, Yin-Hua; Feng, You-Ji
- Abstract
Objective: To determine the role of oestrogen receptor α (ERα) in the regulation of survivin expression by 17β-estradiol (E) in ovarian cancer cells and to evaluate the mechanism of E 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, 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. Pre-treatment with ICI 182780 attenuated the up-regulation of survivin by E. Previous data from our laboratory showed that E 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 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.
- Subjects
ESTROGEN receptors; ESTRADIOL; OVARIAN cancer; CANCER cell motility; SURVIVIN (Protein); CELL lines; WESTERN immunoblotting
- Publication
Archives of Gynecology & Obstetrics, 2012, Vol 286, Issue 3, p729
- ISSN
0932-0067
- Publication type
Article
- DOI
10.1007/s00404-012-2368-5