Differential regulation of albumin gene expression by heparin-binding epidermal growth factor-like growth factor in alpha-fetoprotein-producing and -nonproducing human hepatoma cells.
The effects of heparin-binding epidermal growth factor-like growth factor (HB-EGF) on albumin gene expression were analyzed in alpha-fetoprotein (AFP)-producing and AFP-nonproducing human hepatoma cells, HuH-7 and huH-1/cl.2, in which the AFP silencer is inactive and active, respectively. HB-EGF selectively suppressed the AFP enhancer activity, resulting in decreased levels of both albumin and AFP mRNA in HuH-7 cells. In contrast, HB-EGF did not influence the albumin transcripts in huH-1/cl.2 cells or primary culture of rat hepatocytes, although the AFP enhancer activity was reduced by HB-EGF in huH-1/cl.2 cells as well as in HuH-7 cells. These results indicate that the AFP silencer interacts with the AFP enhancer to block its activity regulating both the albumin and AFP promoters, and that HB-EGF downregulates the albumin gene expression only in the absence of the AFP silencer through the repression of the AFP enhancer activity.
Ishikawa
H
H
First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Nakata
K
K
Tsuruta
S
S
Nakao
K
K
Kato
Y
Y
Tamaoki
T
T
Eguchi
K
K
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004742:Enhancer Elements, Genetic; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012709:Serum Albumin / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000096:biosynthesis* / Q000235:genetics
C587883:HBEGF protein, human; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D000509:alpha-Fetoproteins; D004815:Epidermal Growth Factor