HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology



Review

Alteration of cell-cycle related genes in hepatocarcinogenesis

N. Nishida1, Y. Fukuda1, K. Ishizaki2 and K. Nakao1

1Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto and 2Laboratory of Experimental Radiology, Aichi Cancer Center Research Institute, Chigusaku, Nagoya, Japan

Offprint requests to: Dr. Naoshi Nishida. Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto 606, Japan

 

Summary. The mammalian cell cycle is controlled by regulators of the G1 to S transition such as tumor suppressor proteins, p53 and retinoblastoma (RB); cyclin D1 and cyclin-dependent kinase 4; and inhibitor of cyclin dependent kinase, Recently, aberrations of these cell cycle-related genes have been reported to contribute to the formation and development of cancer. In human hepatocellular carcinoma (HCC), high frequencies of aberration have been detected in the p53 and RB genes. Loss of heterozygosity (LOH) of chromosome 13q was detected in 35% of HCC and LOH on chromosome 17p was detected in 49%. Mutation of the p53 gene was also detected in 32%. The aberrations of these genes were observed more frequently in poorly differentiated and in advanced HCCs. On the other hand, genetic alterations of the cyclin DI and p161NK4A genes were not so frequent, but appeared to be associated with the aggressive behavior of the tumor, which suggests that disruption of the cell cycle-related genes results in the progression of HCC. Further study with a substantial number of cases is required to determine the actual frequency of the aberrations of the G1 controlling genes in hepatocarcinogenesis. Histol Histopathol 12, 1019-1025 (1997)

 

Key words: p53, RB, Cyclin DI, p16, Hepatocellular carcinoma

DOI: 10.14670/HH-12.1019