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Published in: Archives of Gynecology and Obstetrics 3/2012

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.
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Metadata
Title
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
Publication date
01-09-2012
Publisher
Springer-Verlag
Published in
Archives of Gynecology and Obstetrics / Issue 3/2012
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-012-2368-5

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