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Journal of Endocrinology (2009) 202, 167-177       DOI: 10.1677/JOE-09-0054
© 2009 Society for Endocrinology
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Differential induction of LRP16 by liganded and unliganded estrogen receptor {alpha} in SKOV3 ovarian carcinoma cells

 Liyuan Tian1,*, Zhiqiang Wu1,*, Yali Zhao1,*, Yuanguang Meng2, Yiling Si1, Xiaobing Fu1, Yiming Mu3 and Weidong Han1

Departments of
1 Molecular Biology, Institute of Basic Medicine
2 , Obstetrics and Gynecology
3 Endocrinology, Chinese PLA General Hospital, Beijing 100853, People's Republic of China

(Correspondence should be addressed to W Han; Email: hanwdrsw69{at}yahoo.com)

* (L Tian, Z Wu and Y Zhao contributed equally to this work)

Previously, we investigated the induction effect of LRP16 expression by estrogen (17β-estradiol, E2) and established a feed-forward mechanism that activated estrogen receptor {alpha} (ER{alpha}) transactivation in estrogen-dependent epithelial cancer cells. LRP16 is required for ER{alpha} signaling transduction by functioning as an ER{alpha} coactivator. In this study, we demonstrated that LRP16 expression was upregulated in E2-responsive BG-1 ovarian cancer cells, but was downregulated in estrogen-resistant SKOV3 ovarian cancer cells. Pure estrogen antagonist ICI 182 780 did not affect LRP16 expression in SKOV3 cell. The unliganded ER{alpha} upregulated 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{alpha} at LRP16 promoter in the absence of estrogen; however, ER{alpha} was largely released from the DNA upon E2 stimulation. Modulation in 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{alpha} 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.






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