Expression of heparin-binding epidermal growth factor-like growth factor in the hepatocytes of fibrotic rat liver during hepatocarcinogenesis.

Abstract

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. 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. 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. 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.