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The Korean Journal of Pathology 2003;37(4): 255-262.
Expression of Cyclins (D1, A, E, and B1) in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis.
Gui Young Kwon, Eon Sub Park, Sung Geun Bong, Tae Jin Lee, Mi Kyung Kim, Jae Hyung Yoo, Kye Yong Song
Department of Pathology, Chung-Ang University College of Medicine, Seoul, Korea. taejlee@chol.com
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 throughhyperplasia, papilloma, and carcinoma (p<0.01). Expressions of cyclin D1, B1 and cyclin Ewere higher in invasive carcinomas than in superficial carcinomas (p<0.01). In contrast, therewas no significant difference in the expression of cyclin B1 between hyperplasia, papillomaand 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. Aberrantexpression of cyclin B1 and E may contribute to the progression from superficial to invasivebladder cancer rather than tumorigenesis.
Key Words: Cyclins; Carcinogenesis; N-butyl-(4-hydroxybutyl)nitrosamine; Rat; Urinary bladder