title: 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.
authors.affiliation: Inserm Equipe Avenir, U540, 60 rue de Navacelles, Montpellier, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Annicotte
authors.forename: Carine
authors.initials: C
authors.lastname: Chavey
authors.forename: Nadège
authors.initials: N
authors.lastname: Servant
authors.forename: Jacques
authors.initials: J
authors.lastname: Teyssier
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bardin
authors.forename: Anne
authors.initials: A
authors.lastname: Licznar
authors.forename: Eric
authors.initials: E
authors.lastname: Badia
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.forename: Françoise
authors.initials: F
authors.lastname: Vignon
authors.forename: Thierry
authors.initials: T
authors.lastname: Maudelonde
authors.forename: Gwendal
authors.initials: G
authors.lastname: Lazennec
authors.forename: Vincent
authors.initials: V
authors.lastname: Cavailles
authors.forename: Lluis
authors.initials: L
authors.lastname: Fajas
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; C082631:NR5A2 protein, human; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors