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

2005; Springer Nature; Volume: 24; Issue: 55 Linguagem: Inglês

10.1038/sj.onc.1208950

1476-5594

Jean‐Sébastien Annicotte, Carine Chavey, Nadège Servant, Jacques Teyssier, Aurélie Bardin, Anne Licznar, Éric Badia, Pascal Pujol, Françoise Vignon, Thierry Maudelondé, Gwendal Lazennec, Vincent Cavaillès, Lluís Fajas,

Cholesterol and Lipid Metabolism

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) α expressing cell lines, whereas weak-to-no expression was found in nonexpressing ERα cell lines. In MCF7, LRH-1 expression was highly induced after treatment with 17β-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 α and reinforce the hypothesis that LRH-1 could exert potential oncogenic effects during breast cancer formation.