PT - JOURNAL ARTICLE AU - Ding, Jingxin AU - Feng, Youji AU - Yin, Lianhua AU - Jin, Hongyan AU - Liu, Xiaoxia AU - Yao, Liangqing AU - Sun, Yunyan TI - The Effect of 17β–Estradiol on Invasion by the Ovarian Clear Cell Adenocarcinoma Cell Line ES –2 and the Molecular Mechanism Involved DP - 2005 Aug 01 TA - Chinese Journal of Clinical Oncology PG - 717--725 VI - 2 IP - 4 4099 - http://www.cancerbiomed.org/content/2/4/717.short 4100 - http://www.cancerbiomed.org/content/2/4/717.full SO - Cancer Biol Med2005 Aug 01; 2 AB - OBJECTIVE To assess the effect of 17β–estradiol(E2) on cell proliferation, cell invasiveness and its regulation of MTA3, Snail and matrix metalloproteinase 2 (MMP–2) expression in the ovarian clear cell adenocarcinoma cell line ES–2, and to further investigate the mechanism involved.METHODS We first investigated expression of ERα, ERβ, PR and E-cadherin of ES–2 cells by RT–PCR and Western blots. Before all experiments, the ES–2 cells were grown in medium depleted of steroid for more than 7 days. Following treatment with 10−7, 10−8 and 10−9M E2, cell viability of the ES–2 cells was determined by the MTT method, and the cell cycle distribution and apoptosis were examined by flow cytometry (FCM). Invasion and mobility assays were performed using modified Boyden chambers. MTA3, Snail and MMP –2 mRNA expression was measured by RT –PCR, and Snail, MMP –2 protein levels were determined by IHC. MMP –2 activity was assayed by zymography.RESULTS RT –PCR and Western Blots showed that the expression of ERα and E –cadherin mRNA and protein in the ES –2 cells was negative, while ERβ and PR expression was positive. E2 at 10−7,10−8 or 10−9M stimulated cell proliferation. A level of 10−8M E2 reduced the proportion of G0–G1 phase cells and increased the proportion of cells in the S phase, but it had no effect on apoptosis. Invasiveness and mobility of the ES–2 cells was significantly increased by 10−8M E2. Treatment with 10−8M E2 led to reduced MTA3 mRNA expression, and elevated Snail and MMP–2 mRNA and protein levels.CONCLUSION E2 enhanced invasion by the ES–2 cells. The effects observed maybe mediated by down-regulation of MTA3 and up-reguation of Snail and MMP–2.