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KMID : 0357920030370040255
Korean Journal of Pathology
2003 Volume.37 No. 4 p.255 ~ p.262
Expression of Cyclins (D1, A, E, and B1) in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis
Kwon Gui-Young

Park Eon-Sub
Bong Sung-Geun
Lee Tae-Jin
Kim Mi-Kyung
Yoo Jae-Hyung
Song Kye-Yong
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. Expression 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.
KEYWORD
Cyclins, Carcinogenesis, N-butyl-(4-hydroxybutyl)nitrosamine, Rat, Urinary bladder
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