Expression of heparin-binding epidermal growth factor-like growth factor in the hepatocytes of fibrotic rat liver during hepatocarcinogenesis.
BACKGROUND
Heparin-binding epidermal growth factor-like growth factor is an hepatotrophic factor expressed in non-parenchymal liver cells but not in hepatocytes in regenerating rat liver after partial hepatectomy. Human hepatocellular carcinoma cells also produce this growth factor. In this study, the expression of the growth factor in the hepatocytes of fibrotic liver during hepatocarcinogenesis was investigated.


METHODS
Hepatic fibrosis was induced in rats by oral administration of 0.05% thioacetamide. Hepatocytes were isolated by in situ perfusion methods. Growth factor gene and protein expression were investigated by northern hybridization and immunohistochemistry, respectively. Expression of glutathione s-transferase P, which is expressed when hepatocytes undergo neoplastic transformation, was also investigated.


RESULTS
Some hepatocytes in fibrotic liver, but not in normal liver, stained positively by immunohistochemistry for heparin-binding epidermal growth factor-like growth factor. The growth factor and glutathione s-transferase P gene transcript were present in hepatocytes isolated from fibrotic liver, but not in those isolated from normal liver. Immunohistochemical localization of both proteins in fibrotic liver revealed similar patterns.


CONCLUSIONS
In essence, hepatocytes in fibrotic rat liver produce heparin-binding epidermal growth factor-like growth factor. Expression of this growth factor may occur as hepatocytes are transformed to a neoplastic phenotype.
Kiso
S
S
Second Department of Internal Medicine, Osaka University Medical School, Japan. kiso@imed2.med.osaka-u.ac.jp
Kawata
S
S
Tamura
S
S
Miyagawa
J
J
Ito
N
N
Tsushima
H
H
Yamada
A
A
Umeki
S
S
Higashiyama
S
S
Taniguchi
N
N
Matsuzawa
Y
Y
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide
C587883:HBEGF protein, human; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D013853:Thioacetamide; D004815:Epidermal Growth Factor; D005982:Glutathione Transferase