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The nuclear receptor liver receptor homolog-1 is an estrogen receptor target gene.
- Source :
-
Oncogene [Oncogene] 2005 Dec 08; Vol. 24 (55), pp. 8167-75. - Publication Year :
- 2005
-
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.
- Subjects :
- Binding Sites
Breast Neoplasms
Cell Line, Tumor
Disease Progression
Female
Gene Expression Regulation, Neoplastic
Humans
Promoter Regions, Genetic
RNA, Small Interfering genetics
DNA-Binding Proteins genetics
Estrogen Receptor alpha physiology
Receptors, Cytoplasmic and Nuclear genetics
Transcription Factors genetics
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 24
- Issue :
- 55
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 16091743
- Full Text :
- https://doi.org/10.1038/sj.onc.1208950