HEPATOCYTE GROWTH-FACTOR STIMULATES DNA-SYNTHESIS IN RAT PRENEOPLASTIC HEPATOCYTES BUT NOT IN LIVER-CARCINOMA CELLS

Background & Aims: It is not well clarified whether hepatocyte growth factor (HGF) stimulates the growth of preneoplastic hepatocytes and li ver carcinoma cells in vivo. The effect of HGF on in vivo DNA synthesi s in these cells and also its effect on tyrosine phosphorylation of th e HGF receptor protein (c-Met) in liver carcinoma were examined. Metho ds: Lesions were induced in rats using 3'-methyl-4-dimethylaminoazoben zene (3'-Me-DAB). The rats were given intravenous recombinant human HG F or vehicle, and DNA synthesis was assessed by the 5-bromo-2'-deoxyur idine labeling index. Tyrosine phosphorylation of c-Met by HGF was ana lyzed by Western blot. Results: The labeling indices were significantl y higher in the HGF group than in the vehicle control group in altered foci and hyperplastic nodules (preneoplastic hepatic lesions). No sig nificant differences in the labeling indices were observed between the two groups with carcinoma. Tyrosine phosphorylation of c-Met in carci noma cells was unaffected by HGF administration. Conclusions: HGF prom otes the growth of preneoplastic hepatocytes but does not affect the g rowth of liver carcinoma cells in 3'-Me-DAB-treated rats.