Cooperation between the human estrogen receptor (ER) and MCF-7 cell-specific transcription factors elicits high activity of an estrogen-inducible enhancer from the trout ER gene promoter.
Mol Endocrinol
; 10(9): 1116-26, 1996 Sep.
Article
em En
| MEDLINE
| ID: mdl-8885246
ABSTRACT
The human estrogen receptor (hER) is expressed in breast cancer MCF-7 cells and plays a major role in tumorigenic processes. In this report, we demonstrate that MCF-7-specific factors can cooperate with the hER to increase its transactivation activity. We previously demonstrated that the rainbow trout ER (rtER) gene is up-regulated by the rtER protein itself, through an enhancer that contains an imperfect estrogen-responsive element (FP1 area). By performing footprinting experiments, we have delineated two other regulatory regions (FP2 and FP3 areas) in the 0.2-kb enhancer. We show, by transient transfections, that hER poorly transactivates this enhancer in CHO-K1 and Ishikawa cells whereas, in MCF-7 cells, transcriptional activation occurs at a level about 20-fold higher than when the enhancer estrogen-responsive element (FP1) is the only regulatory region included in the reporter gene. These results indicate that areas other than FP1 are important regulatory sites of this enhancer. Site-directed mutagenesis demonstrated that the FP1 area is absolutely necessary for induction by estradiol as well as for basal activity of this enhancer in MCF-7 cells. Gel shift experiments showed that MCF-7 cells contain a factor that binds to the FP3 area and is poorly expressed in all other tested cell lines. As suggested by site-directed mutagenesis and deletion experiments, this FP3-binding protein may enhance the hER transactivation ability in MCF-7 cells. These data reinforce the idea that cell-specific transcription factors cooperate with steroid receptors to achieve maximal induction of hormone-responsive genes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Neoplasias da Mama
/
Receptores de Estrogênio
/
Elementos Facilitadores Genéticos
/
Oncorhynchus mykiss
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article