Expression of the c-met protooncogene in human hepatocellular carcinoma.
The c-met protooncogene is a growth factor receptor with tyrosine kinase activity. Recently the hepatocyte growth factor was identified as the ligand for this receptor. Because the hepatocyte growth factor is a most potent mitogen in hepatocytes, possible involvement of c-met expression in hepatocarcinogenesis is suspected. In this study, we examined c-met expression in 23 hepatocellular carcinoma cases by means of Northern-blot analysis and an immunohistochemical study. Northern-blot analysis revealed c-met mRNA expression in the tumors of 6 of 19 patients (31.6%); in the immunohistochemical study, c-met protein was detected in 16 of 23 patients (69.6%). With both methods, c-met was found to be overexpressed in hepatocellular carcinoma compared with the surrounding normal liver. Comprehensive analysis showed that c-met protein expression was correlated with poor-to-moderate differentiation of cancer cells (p < 0.05). Tumor proliferative activity of hepatocellular carcinoma was evaluated by means of Ki-67 labeling index. All cases with increased tumor proliferative activity showed c-met protein expression, although the elevation of proliferative activity in the c-met-positive group was not statistically significant. These data suggest that the overexpression of c-met plays an important role in the development of hepatocellular carcinoma.
Suzuki
K
K
First Department of Medicine, Osaka University Medical School, Japan.
Hayashi
N
N
Yamada
Y
Y
Yoshihara
H
H
Miyamoto
Y
Y
Ito
Y
Y
Ito
T
T
Katayama
K
K
Sasaki
Y
Y
Ito
A
A
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases