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

Autor: Nadège Servant, Vincent Cavaillès, Anne Licznar, Jean-Sébastien Annicotte, Gwendal Lazennec, Pascal Pujol, Françoise Vignon, Aurélie Bardin, Thierry Maudelonde, Carine Chavey, Jacques Teyssier, Lluis Fajas, Eric Badia
Přispěvatelé: Le Ster, Yves, Endocrinologie moléculaire et cellulaire des cancers, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Muscle et pathologies, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Cellulaire et Hormonale, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve
Jazyk: angličtina
Rok vydání: 2005
Předmět:
Cancer Research
Transcription
Genetic

Estrogen receptor
Receptors
Cytoplasmic and Nuclear

Estrogen-related receptor alpha
0302 clinical medicine
E2
Nuclear receptors
MESH: RNA
Small Interfering

RNA
Small Interfering

Promoter Regions
Genetic

MESH: Estrogen Receptor alpha
Nuclear receptor co-repressor 1
0303 health sciences
MESH: Gene Expression Regulation
Neoplastic

Cell biology
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic

MESH: Promoter Regions (Genetics)
030220 oncology & carcinogenesis
Interleukin-21 receptor
Disease Progression
Female
MESH: Disease Progression
Transcription
medicine.medical_specialty
MESH: Cell Line
Tumor

MESH: Receptors
Cytoplasmic and

Breast Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
Article
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
Internal medicine
Cell Line
Tumor

Breast Cancer
Genetics
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology

Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology

Molecular Biology
Estrogen receptor beta
030304 developmental biology
Binding Sites
MESH: Humans
Liver receptor homolog-1
Estrogen Receptor alpha
Ftz-F1
Endocrinology
MESH: Binding Sites
Estrogen-related receptor gamma
Gene expression
Estrogen receptor alpha
MESH: Female
LRH-1
MESH: Breast Neoplasms
MESH: DNA-Binding Proteins
Transcription Factors
Zdroj: Oncogene
Oncogene, Nature Publishing Group, 2005, 24 (55), pp.8167-75. ⟨10.1038/sj.onc.1208950⟩
ISSN: 0950-9232
1476-5594
DOI: 10.1038/sj.onc.1208950⟩
Popis: International audience; 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.
Databáze: OpenAIRE