N-butyl- N-(4-hydroxybutyl)nitrosamine에 의한 흰쥐 방광암 발생 과정에서 세포주기 관련인자 단백(Cyclin D1, A, E, and B)의 발현

Abstract

Background : Cell cycle deregulation plays a major role in chemical multistage carcinogenesis. Therefore, the evaluation of cell cycle proteins is important. Methods : In order to induce carcinogenesis in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) was administered to male Sprague-Dawley rats for 30 weeks. Expressions of cyclin D1, A, E, and B1 were examined by immunohistochemical stainings. Results : Urothelial cell hyperplasia appeared at 5 weeks, followed by papilloma at 10 weeks. Superficial carcinoma was observed at 20 weeks, and invasive carcinoma developed in 40% (4/10) of the rats at 30 weeks. Expressions of cyclin D1 and A increased sequentially from normal mucosa through hyperplasia, papilloma, and carcinoma (p<0.01). Expressions of cyclin D1, B1 and cyclin E were higher in invasive carcinomas than in superficial carcinomas (p<0.01). In contrast, there was no significant difference in the expression of cyclin B1 between hyperplasia, papilloma and superficial carcinoma. Conclusions : The present results indicate the important roles of cyclin D1 and A in the development of BBN-induced urothelial carcinoma of rats. Aberrant expression of cyclin B1 and E may contribute to the progression from superficial to invasive bladder cancer rather than tumorigenesis.