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

Oncogene volume 24, pages 8167–8175 (2005)Cite this article

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) 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.

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Acknowledgements

Helpful discussions with Dr M Esslimani-Sahla and members of the Fajas lab are greatly appreciated. We thank Fanja Rabeolina for excellent technical help and the Vector Core of the University Hospital of Nantes for the production of adenovirus. This work was supported by grants from INSERM, CHU de Montpellier, Association pour la Recherche contre le Cancer, and Fondation pour la Recherche Médicale. JSA is supported by post-doctoral fellowships from the Ligue Nationale Contre le Cancer (2004) and the INSERM (2005). CC is supported by a post-doctoral fellowship from the Ligue Nationale Contre le Cancer. This work is dedicated to the memory of the coauthor F Vignon, deceased while the manuscript was in preparation.

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Authors and Affiliations

  1. Inserm Equipe Avenir, U540, 60 rue de Navacelles, Montpellier, France

    Jean-Sébastien Annicotte, Carine Chavey, Nadège Servant, Jacques Teyssier, Aurélie Bardin, Anne Licznar, Eric Badia, Pascal Pujol, Françoise Vignon, Thierry Maudelonde, Gwendal Lazennec, Vincent Cavailles & Lluis Fajas

  2. Inserm Equipe Avenir, Montpellier, F-34090, France

    Jean-Sébastien Annicotte, Nadège Servant, Jacques Teyssier & Lluis Fajas

  3. Laboratoire de Biologie Cellulaire, Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, F-34090, France

    Pascal Pujol, Thierry Maudelonde & Lluis Fajas

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  1. Jean-Sébastien Annicotte
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  2. Carine Chavey
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  13. Lluis Fajas
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Correspondence to Lluis Fajas.

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Annicotte, JS., Chavey, C., Servant, N. et al. The nuclear receptor liver receptor homolog-1 is an estrogen receptor target gene. Oncogene 24, 8167–8175 (2005). https://doi.org/10.1038/sj.onc.1208950

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  • DOI: https://doi.org/10.1038/sj.onc.1208950

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