Abstract
Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes; however, in certain human hepatoma cell lines, the growth is inhibited by HGF. In the present study, the effect of HGF on the alpha-fetoprotein (AFP) gene expression was analyzed in PLC/PRF/5 human hepatoma cells. HGF did not inhibit cell proliferation, but dose-dependently suppressed AFP secretion at the concentrations of 10 ng/ml or less. By Northern blot analysis, the levels of AFP mRNA were suppressed by HGF, whereas the levels of beta-actin mRNA used as a control did not show any significant changes. In the transient chloramphenicol acetyltransferase plasmid transfection assays, the AFP promoter activity was repressed by HGF, in contrast, the AFP enhancer activity was not affected by HGF. These results suggest that the AFP gene expression is down-regulated by HGF through the suppression of its promoter activity in human hepatoma cells.
MeSH terms
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Animals
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Blotting, Northern
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CHO Cells
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Carcinoma, Hepatocellular
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Cell Division / drug effects
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Chloramphenicol O-Acetyltransferase / genetics
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Chloramphenicol O-Acetyltransferase / isolation & purification
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Chloramphenicol O-Acetyltransferase / metabolism
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Cricetinae
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DNA, Neoplasm / biosynthesis
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Neoplastic / drug effects*
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Hepatocyte Growth Factor / pharmacology*
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Humans
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Kinetics
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Liver Neoplasms
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RNA, Neoplasm / genetics
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RNA, Neoplasm / isolation & purification
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / isolation & purification
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Recombinant Proteins / pharmacology
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Transfection
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Tumor Cells, Cultured
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alpha-Fetoproteins / biosynthesis*
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alpha-Fetoproteins / genetics
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alpha-Fetoproteins / isolation & purification
Substances
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DNA, Neoplasm
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RNA, Neoplasm
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Recombinant Fusion Proteins
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Recombinant Proteins
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alpha-Fetoproteins
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Hepatocyte Growth Factor
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Chloramphenicol O-Acetyltransferase