Circadian variations of clock gene Per2 and cell cycle genes in different stages of carcinogenesis in golden hamster buccal mucosa

Previous studies have suggested that the expression of clock genes have circadian rhythms, and many cell cycle genes are regulated by clock genes. The disruption of circadian rhythms appears to be associated with the acceleration of cancer development. To investigate the circadian patterns of the clock gene Per2 and of cell cycle genes p53, Cyclin D1, CDK1 and Cyclin B1 in different stages of carcinogenesis, the daily mRNA profiles of these genes were detected by real-time RT-PCR in dimethylbenzanthracene-induced cancer, in precancerous lesions and in normal tissues. Per2, p53, Cyclin D1 and CDK1 showed circadian rhythms in the 3 different stages of carcinogenesis, whereas the circadian rhythm of Cyclin B1 was absent in the precancerous lesions. The mesors and amplitudes of Per2 and p53 were decreased (P < 0.05), but the mesors of Cyclin D1, CDK1 and Cyclin B1 were increased with the development of cancer (P < 0.05). Compared with the normal tissues, the acrophases of Per2 and CDK1 were earlier in precancerous lesions, and the acrophases of Cyclin D1, CDK1 and Cyclin B1 occurred later in the cancer cells. Our study represents the first demonstration of the circadian pattern variations of these genes in different stages of carcinogenesis.