Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma.
We analyzed the genetic alterations of the cyclin D1 and INT-2 genes in hepatocellular carcinomas (HCCs) from 45 patients. Among these, expression of the cyclin D1 mRNA was also analyzed in 18 of them by Northern blotting. The cyclin D1 gene was amplified 3-16 fold in five HCCs (11%); among these, the INT-2 gene was also amplified 2-10 fold in four HCCs. We analyzed the mRNA of cyclin D1 in four HCCs with gene amplifications, and 6-10 fold overexpressions were detected in all of them. Because the cyclin D1 gene was amplified in patients at an advanced stage of HCC with rapid tumor growth, it appeared to be associated with the aggressive behavior of tumors. Studies on loss of heterozygosity on chromosome 13q, where the retinoblastoma (RB) gene is located, indicated that all HCCs with an amplified cyclin D1 gene retained heterozygosity on chromosome 13q. These results suggest that amplification and overexpression of the cyclin D1 gene result in the rapid growth of a subset of HCC, even though the function of the RB gene is retained.
Nishida
N
N
Radiation Biology Center, Kyoto University, Japan.
Fukuda
Y
Y
Komeda
T
T
Kita
R
R
Sando
T
T
Furukawa
M
M
Amenomori
M
M
Shibagaki
I
I
Nakao
K
K
Ikenaga
M
M
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D016213:Cyclins; C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D019938:Cyclin D1; D005346:Fibroblast Growth Factors