|Budget Amount *help
¥1,600,000 (Direct Cost : ¥1,600,000)
Fiscal Year 1994 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1993 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Gene expression, amplification and rearrangement of c-met gene (receptor gene for hepatocyte growth factor, HGF) were examined in order to elucidate whether c-met gene was associated with hepatocarcinogenesis
Liver cirrhosis (LC) , precarcinomatous hepatic lesion and carcinomatous hepatic lesion were developed by administration of carbontetrachloride, diethlnitrosamine (DEN) and 3'-Me- DAB,respectively, in rats. Expression of c-met gene was analyzed by Northern blot method. The tpr-met oncogene was examined by Southern blot analysis of amplified 205 bp of cDNA including tpr-met breakpoint by RT-PCR using internal probe. Amplification of c-met gene was analyzed by Southern blot method. Expression of HGF receptor protein (HGF receptor) was analyzed by immunofluorescence antibody method using cryostat sections and anti-c-met antibody.
Expression of c-met gene was slightly increased in LC compared with normal control, and increased 1.5 to 2.0-fold in prehepatocarcinoma and hepatocarcinoma. Amplification of c-met gene was not detected in LC and prehepatocarcinoma, whereas c-met gene was amplified 2 to 7-fold in 2/3 of hepatocarcinoma rats. The tpr-met gene was not detected in these three lesions. Expression of HGF receptor protein was not increased in LC and prehepatocarcinoma, whereas that was increased in some of hepatocarcinoma rats.
In conclusion, it was suggested that increased expression of c-met gene was associated with prehepatocarcinoma and hepatocarcinoma induced by DEN and 3'-Me-DAB,respectively, and gene amplification might be a cause of increased expression of c-met gene in 3'-Me-DAB-induced hepatocarcinoma.