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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0054v1 202/1/167    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tian, L. Articles by Han, W. Search for Related Content PubMed PubMed Citation Articles by Tian, L. Articles by Han, W.

L Tian, Dept. of Molecular Biology, Institute of Basic Medicine, Beijing , China
Z Wu, Dept. of Molecular Biology, Institute of Basic Medicine, Beijing , China
Y Zhao, Dept. of Molecular Biology, Institute of Basic Medicine, Beijing , China
Y Meng, Dept. of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing , China
Y Si, Dept. of Molecular Biology, Institute of Basic Medicine, Beijing , China
X Fu, Dept. of Molecular Biology, Institute of Basic Medicine, Beijing , China
Y Mu, Dept. of Endocrinology, Chinese PLA General Hospital, Beijing , China
W Han, Dept. of Molecular Biology, Chinese PLA General Hospital, Beijing, 100853, China

Correspondence: Weidong Han, Email: hanwdrsw69{at}yahoo.com

Previously, we investigated the induction effect of LRP16 expression by estrogen (E2) and established a feed-forward mechanism that activated ER transactivation in estrogen-dependent epithelial cancer cells. LRP16 is required for ER signaling transduction by functioning as an ER coactivator. In this study, we demonstrated that LRP16 expression was up-regulated in E2-responsive BG-1 ovarian cancer cells, but was down-regulated in estrogen-resistant SKOV3 ovarian cancer cells. Pure estrogen antagonist ICI 182 780 did not affect LRP16 expression in SKOV3 cell. The unliganded ER up-regulated LRP16 expression and enhanced LRP16 promoter activity in SKOV3 cells; however, this induction was blocked by estrogen stimulation. Results from chromatin immunoprecipitation experiment revealed a strong recruitment of the unliganded ER at LRP16 promoter in the absence of estrogen; however, ER was largely released from the DNA upon E2 stimulation. Modulation of LRP16 expression level did not significantly change the proliferation rate of SKOV3 cells and the growth responsiveness of cells to E2. Knockdown of LRP16 by RNA interference in SKOV3 cells markedly attenuated estrogen response element-dependent ER reporter gene activity and E2-induced c-myc expression. Our study suggests a novel mechanism of estrogen resistance of ovarian cancer by which estrogen-repressed signaling pathway antagonizes estrogen-activated signaling transduction.