N,N-diethylnitrosamine에 의해 유도된 흰쥐 간세포암종 발생과정에서 세포주기 관련 유전자 단백(Cyclin D1, Rb, p21&p53)발현에 대한 연구

Abstract

Aberration of cell cycle-related genes have been reported to contribute the formation and development of cancers. To determine the role of cell cyclerelated gene alteration in hepatic carcinogenesis, the expression of cell cycle regulatory gene products (cyclin D1, Rb, p16, p21 and p53) was investigated immuneohistochemically in the altered cell foci and hepatocellular carcinoma induced by DEN. Male rats Sprague-Dawley with body weight 210~220 gm, fed with daily oral intake of drinking water at low dose (120 ppm DEN). The clear cell nodule appeared first at the 3rd week after DEN administration followed acidophilic, and basophilic cell nodules and evident hepatocellular carcinoma foci were appeared after 15 weeks of DEN administration. Rb, p16 and p21 proteins showed only intracytoplasmic positive reaction in hyperplastic nodules, and hepatocelllular carcinoma showed p53 positive reaction only. Cyclin D1 expression appeared first at the 3rd week after DEN-treated group, gradually increased to the 12th week, continuing to the hepatocellular carcinoma. The strong positive reaction of cyclin D1 was noted at the proliferating cells around the hepatocellular carcinoma. The results suggest that the cylin D1 overexpression contribute an early hepatic carcinogenesis induced by DEN in rat. However, further molecular genetic studies for the determination of relationships in expression of other cell cycle-related gene proteins were required.