Citation
- Authors: Annicotte, J. S., Chavey, C., Servant, N., Teyssier, J., Bardin, A., Licznar, A., Badia, E., Pujol, P., Vignon, F., Maudelonde, T., Lazennec, G., Cavailles, V., Fajas, L.
- Year: 2005
- Journal: Oncogene 24 8167-75
- Applications: in vitro / DNA / jetPEI
- Cell types:
- Name: BT-20
- Name: BT-474
Description: Human breast ductal carcinoma cells - Name: CAMA-1
- Name: MCF7
Description: Human breast adenocarcinoma cells
Known as: MCF-7, MCF 7 - Name: MDA-MB-231
Description: Human breast adenocarcinoma cells
Known as: MDAMB231 - Name: MDA-MB-435
Description: Human breast cancer cells - Name: MDA-MB-468
- Name: SK-BR-3
Description: Human mammary gland adenocarcinoma - Name: T-47D
Description: Human breast ductal carcinoma cells
Known as: T 47 - Name: ZR75
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.