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¹ Departments of Molecular Biology, Institute of Basic Medicine,
² Obstetrics and Gynecology and
³ Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
⁴ Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan

(Correspondence should be addressed to Y-M Mu; Email: muyiming{at}301hospital.com.cn)

Previous studies have shown that leukemia related protein 16 (LRP16) is estrogenically regulated and that it can stimulate the proliferation of MCF-7 breast cancer cells, but there are no data on the mechanism of this pathway. Here, we demonstrate that the LRP16 expression is estrogen dependent in several epithelium-derived tumor cells. In addition, the suppression of the endogenous LRP16 in estrogen receptor (ER)-positive MCF-7 cells not only inhibits cells growth, but also significantly attenuates the cell line’s estrogen-responsive proliferation ability. However, ectopic expression of LRP16 in ER-negative MDA-MB-231 cells has no effect on proliferation. These data suggest the involvement of LRP16 in estrogen signaling. We also provide novel evidence by both ectopic expression and small interfering RNA knockdown approaches that LRP16 enhances ER-mediated transcription activity. In stably LRP16-inhibitory MCF-7 cells, the estrogen-induced upregulation of several well-known ER target genes including cyclin D1 and c-myc is obviously impaired. Results from glutathione S-transferase pull-down and coimmunoprecipitation assays revealed that LRP16 physically interacts with ER in a manner that is estrogen independent but is enhanced by estrogen. Furthermore, a mammalian two-hybrid assay indicated that the binding region of LRP16 localizes to the A/B activation function 1 domain of ER. Taken together, these results present new data supporting a role for estrogenically regulated LRP16 as an ER coactivator, providing a positive feedback regulatory loop for ER signal transduction.

This article has been cited by other articles:

				L. Tian, Z. Wu, Y. Zhao, Y. Meng, Y. Si, X. Fu, Y. Mu, and W. Han Differential induction of LRP16 by liganded and unliganded estrogen receptor {alpha} in SKOV3 ovarian carcinoma cells J. Endocrinol., July 1, 2009; 202(1): 167 - 177. [Abstract] [Full Text] [PDF]

				J Yang, Y-L Zhao, Z-Q Wu, Y-L Si, Y-G Meng, X-B Fu, Y-M Mu, and W-D Han The single-macro domain protein LRP16 is an essential cofactor of androgen receptor Endocr. Relat. Cancer, March 1, 2009; 16(1): 139 - 153. [Abstract] [Full Text] [PDF]