Transcriptional activation of insulin-like growth factor binding protein 6 by 17beta-estradiol in SaOS-2 cells
Experimental & Molecular Medicine
;
: 478-486, 2009.
Artículo
en Inglés
| WPRIM
| ID: wpr-107288
ABSTRACT
Osteoblasts can synthesize the insulin-like growth factors (IGFs) and the IGF-binding proteins (IGFBPs), which may either enhance or attenuate IGF-stimulated bone cell proliferation. Since estrogen induced osteoblastic differentiation and proliferation through an estrogen-responsive gene in target cells, we investigated the effects of estrogen on IGFBP-6 expression in the human osteoblastic-like cell line SaOS-2. Expressions of IGFBP-6 protein and mRNA increased 2.8 and 2-fold, respectively, in the presence of 17-beta-estradiol (E2) (0.01 to 1 micrometer) and estrogen receptor (ER) in SaOS-2 cells. On the other hand, E2 induced a 2-fold increase in SaOS-2 cell proliferation. To identify genomic sequences associated with estrogen responsiveness, the 5'-promoter region (-44 to +118) of the IGFBP-6 gene was cloned into a chloramphenicol acetyltransferase (CAT) reporter vector. E2 induced a 3-fold increase in CAT activity in SaOS-2 cells transiently transfected with this construct. Identification of the estrogen-responsive element (ERE) [5'-CCTTCA CCTG-3'] (-9 to +1) in this IGFBP-6 gene promoter region was confirmed using electromobility shift assays and deletion analysis. This functional ERE was important for E2-induced trans-activation of the IGFBP-6 gene. These results demonstrate that E2 exhibits a positive effect on IGFBP-6 gene transcription through estrogen-liganded ER binding to the functional ERE in the IGFBP-6 gene promoter in SaOS-2 cells.
Texto completo:
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Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Osteoblastos
/
ARN Mensajero
/
Células Tumorales Cultivadas
/
Cloranfenicol O-Acetiltransferasa
/
Activación Transcripcional
/
Western Blotting
/
Regiones Promotoras Genéticas
/
Proteína 6 de Unión a Factor de Crecimiento Similar a la Insulina
/
Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
/
Elementos de Respuesta
Tipo de estudio:
Estudio pronóstico
Límite:
Humanos
Idioma:
Inglés
Revista:
Experimental & Molecular Medicine
Año:
2009
Tipo del documento:
Artículo
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