Involvement of Egr-1 in HGF-induced elevation of the human 5alpha-R1 gene in human hepatocellular carcinoma cells
Abstract
Steroid 5alpha-reductase 1 (5alpha-R1), a key enzyme in the conversion of steroids into their respective 5alpha-reduced derivatives, plays a key role in some hormone-dependent tumours and is abundant in the liver, although it is also widely distributed throughout the body. HGF (hepatocyte growth factor) is a pleiotropic cytokine/growth factor involved in the progression of hepatocellular carcinoma. In the present paper, we report the stimulatory effect of HGF on human 5alpha-R1 transcription in hepatocellular carcinoma cells. Pre-treatment with actinomycin D or cycloheximide blocked the up-regulation of 5alpha-R1 mRNA expression by HGF, indicating that the increased level of 5alpha-R1 mRNA expression is regulated by transcriptional activation and was dependent on de novo protein synthesis. Functional analysis of the 5'-flanking region of the 5alpha-R1 gene by transfection analysis showed that the -79 to -50 region functioned as the HGF-responsive region. Mutagenesis and electrophoretic mobility-shift assays demonstrated that induction of 5a-R1 by HGF is mediated by an Egr-1 (early growth-response gene 1)-binding site at -60/-54. In addition, overexpression of Egr-1 was sufficient to transactivate 5alpha-R1 promoter activity, an...Continue Reading
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Carcinoma, Hepatocellular
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