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KMID : 0620920090410070478
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Experimental & Molecular Medicine
2009 Volume.41 No. 7 p.478 ~ p.486
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Transcriptional activation of insulin-like growth factor binding protein 6 by 17β-estradiol in SaOS-2 cells
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Zhao Yu-Yan
Guo Lei
Zhao Xiao-Juan
Liu Hong
Lei Tian
Ma Dong-Jie
Gao Xiao-Yu
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Abstract
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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-β-estradiol (E2) (0.01 to 1 μM) 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.
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KEYWORD
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estrogen, insulin-like growth factor binding protein 6, osteoblasts, receptors, estrogen, transcription, genetic
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