Korean J Pathol.  2003 Aug;37(4):255-262.

Expression of Cyclins (D1, A, E, and B1) in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis

• Kwon GY
• Park ES
• Bong SG
• Lee TJ
• Kim MK
• Yoo JH
• Song KY

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.

Keyword

Cyclins; Carcinogenesis; N-butyl-(4-hydroxybutyl)nitrosamine; Rat; Urinary bladder

MeSH Terms

Animals
Carcinogenesis*
Cell Cycle
Cell Cycle Proteins
Cyclin B1
Cyclin D1
Cyclins*
Humans
Hyperplasia
Male
Mucous Membrane
Papilloma
Rats*
Rats, Sprague-Dawley
Urinary Bladder*
Cell Cycle Proteins
Cyclin B1
Cyclin D1
Cyclins