Hepatocyte growth factor stimulates DNA synthesis in rat preneoplastic hepatocytes but not in liver carcinoma cells

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 114; no. 4; pp. 775 - 781
• Main Authors: Ogasawara, Hisataka, Hiramoto, Jun, Takahashi, Masaaki, Shirahama, Keigo, Furusaka, Akihiro, Hiyane, Satoshi, Nakada, Tetsuya, Nagayama, Kazuo, Tanaka, Teruji
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-04-1998; Elsevier
• Subjects: Animals; Biological and medical sciences; Bromodeoxyuridine - metabolism; DNA - biosynthesis; Gastroenterology. Liver. Pancreas. Abdomen; Hepatocyte Growth Factor - pharmacology; Humans; Immunohistochemistry; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Methyldimethylaminoazobenzene; Phosphorylation; Precancerous Conditions - chemically induced; Precancerous Conditions - pathology; Proto-Oncogene Proteins c-met - metabolism; Rats; Tumors; Type C Phospholipases - metabolism; Tyrosine - metabolism; GST-P; HGF; HCC; PKC; 3'-Me-DAB; DEN; LI; BrdU; Immunopathology; Animal model; Rat; Hepatocyte growth factor; Liver; Rodentia; Hepatic disease; DNA synthesis; Experimental study; Carcinogenesis; Biological activity; Vertebrata; Mammalia; Hepatocyte; Digestive diseases; Tumor; Mechanism of action; Comparative study
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1016/S0016-5085(98)70591-8

Background & Aims: It is not well clarified whether hepatocyte growth factor (HGF) stimulates the growth of preneoplastic hepatocytes and liver carcinoma cells in vivo. The effect of HGF on in vivo DNA synthesis in these cells and also its effect on tyrosine phosphorylation of the HGF receptor protein (c-Met) in liver carcinoma were examined.
Methods: Lesions were induced in rats using 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). The rats were given intravenous recombinant human HGF or vehicle, and DNA synthesis was assessed by the 5-bromo-2'-deoxyuridine labeling index. Tyrosine phosphorylation of c-Met by HGF was analyzed by Western blot.
Results: The labeling indices were significantly higher in the HGF group than in the vehicle control group in altered foci and hyperplastic nodules (preneoplastic hepatic lesions). No significant differences in the labeling indices were observed between the two groups with carcinoma. Tyrosine phosphorylation of c-Met in carcinoma cells was unaffected by HGF administration.
Conclusions: HGF promotes the growth of preneoplastic hepatocytes but does not affect the growth of liver carcinoma cells in 3'-Me-DAB–treated rats.
GASTROENTEROLOGY 1998;114:775-781