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The nuclear receptor liver receptor homolog-1 is an estrogen receptor target gene.

Abstract : Liver receptor homolog-1 (LRH-1) is a nuclear receptor previously known to have distinct functions during mouse development and essential roles in cholesterol homeostasis. Recently, a new role for LRH-1 has been discovered in tumor progression, giving LRH-1 potential transforming functions. In order to identify critical factors stimulating LRH-1 expression leading to deregulated cellular proliferation, we studied its expression and its regulation in several breast cancer cell lines. We observed that LRH-1 expression was increased in estrogen receptor (ER) alpha expressing cell lines, whereas weak-to-no expression was found in nonexpressing ERalpha cell lines. In MCF7, LRH-1 expression was highly induced after treatment with 17beta-estradiol (E2). This transcriptional regulation was the result of a direct binding of the ER to the LRH-1 promoter, as demonstrated by gelshift and chromatin immunoprecipitation assays. Interestingly, siRNA-mediated inactivation of LRH-1 decreased the E2-dependent proliferation of MCF7 cells. Finally, LRH-1 protein expression was detected by immunohistochemistry in tumor cells of human mammary ductal carcinomas. Altogether, these data demonstrate that LRH-1 is transcriptionally regulated by the ER alpha and reinforce the hypothesis that LRH-1 could exert potential oncogenic effects during breast cancer formation.
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Submitted on : Friday, May 4, 2007 - 1:05:52 PM
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Jean-Sébastien Annicotte, Carine Chavey, Nadège Servant, Jacques Teyssier, Aurélie Bardin, et al.. The nuclear receptor liver receptor homolog-1 is an estrogen receptor target gene.. Oncogene, Nature Publishing Group, 2005, 24 (55), pp.8167-75. ⟨10.1038/sj.onc.1208950⟩. ⟨inserm-00144663⟩



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