Published in:
01-09-2012 | Gynecologic Oncology
Oestrogen receptor α mediates 17β-estradiol enhancement of ovarian cancer cell motility through up-regulation of survivin expression
Authors:
Jing Zhu, Xin Lu, Ke-Qin Hua, Hong Sun, Yin-Hua Yu, You-Ji Feng
Published in:
Archives of Gynecology and Obstetrics
|
Issue 3/2012
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Abstract
Objective
To determine the role of oestrogen receptor α (ERα) in the regulation of survivin expression by 17β-estradiol (E2) in ovarian cancer cells and to evaluate the mechanism of E2 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 E2, 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 E2. Pre-treatment with ICI 182780 attenuated the up-regulation of survivin by E2. Previous data from our laboratory showed that E2 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 E2 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.