Estradiol regulation of the human retinoic acid receptor alpha gene in human breast carcinoma cells is mediated via an imperfect half-palindromic estrogen response element and Sp1 motifs.
Cancer Res
; 55(21): 4999-5006, 1995 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-7585542
ABSTRACT
Estrogen receptor (ER)-positive human breast carcinoma (HBC) cell lines express significantly higher levels of retinoic acid receptor alpha (RAR alpha) (isoform 1) mRNA than ER-negative HBCs. Estradiol enhances RAR alpha mRNA expression in different ER-positive HBCs by 2-3-fold, which in turn results in increased sensitivity of ER-positive HBCs to the growth inhibitory effects of retinoic acid. To investigate the regulatory mechanisms of estradiol-mediated enhancement of RAR alpha mRNA expression, the functional promoter for the human RAR alpha isoform 1 was cloned and used to assess estradiol-mediated promoter-dependent enhancement of firefly luciferase reporter gene activity in transiently transfected ER-positive (MCF-7 and T47D) and ER-negative (MDA-MB-231) HBCs. Deletional promoter constructs were obtained to further delineate the promoter region responsible for estradiol-mediated enhancement of promoter activity. Here, we present evidence that approximately 130 bp of the promoter fragment preceding the transcriptional start site are responsible for estradiol-mediated enhancement of hRAR alpha gene expression. The estradiol-mediated enhancement is dependent on ER binding. Further deletional analysis showed that a promoter sequence of 42 base pairs, located approximately 100 bases upstream of the transcriptional start site, contains elements for estradiol-mediated enhancement. Specific deletion of either the Sp1 motif or mutations in the imperfect half-palindromic estrogen response element motif of this fragment abolish its estradiol responsiveness in transient transfections.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Receptores de Estrogênio
/
Regulação Neoplásica da Expressão Gênica
/
Fator de Transcrição Sp1
/
Regiões Promotoras Genéticas
/
Receptores do Ácido Retinoico
/
Estradiol
Limite:
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos