Linked Life Data

18215136

Source:http://linkedlifedata.com/resource/pubmed/id/18215136

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-3-26
pubmed:abstractText
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, and knockdown of Egr-1 with gene-specific small interfering RNA resulted in inhibition of HGF-induced up-regulation of endogenous 5alpha-R1 expression. These data provide the first evidence that HGF stimulates 5alpha-R1 expression through up-regulation of the transcription factor Egr-1, thus suggesting the possibility that regulation of steroid metabolism by HGF represents a mechanism for high risk of hepatocellular carcinogenesis in males.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
411
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
379-86
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18215136-3-Oxo-5-alpha-Steroid 4-Dehydrogenase, pubmed-meshheading:18215136-Binding Sites, pubmed-meshheading:18215136-Carcinoma, Hepatocellular, pubmed-meshheading:18215136-Cell Line, Tumor, pubmed-meshheading:18215136-Down-Regulation, pubmed-meshheading:18215136-Early Growth Response Protein 1, pubmed-meshheading:18215136-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18215136-Hepatocyte Growth Factor, pubmed-meshheading:18215136-Humans, pubmed-meshheading:18215136-Liver Neoplasms, pubmed-meshheading:18215136-Molecular Sequence Data, pubmed-meshheading:18215136-Promoter Regions, Genetic, pubmed-meshheading:18215136-Protein Binding, pubmed-meshheading:18215136-RNA, Messenger, pubmed-meshheading:18215136-RNA, Small Interfering, pubmed-meshheading:18215136-Transcriptional Activation, pubmed-meshheading:18215136-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Involvement of Egr-1 in HGF-induced elevation of the human 5alpha-R1 gene in human hepatocellular carcinoma cells.
pubmed:affiliation
Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, P.R. China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't