Expression of Transforming Growth Factor-beta1 and Its Receptors in N-butyl-N-(4-hydroxybutyl) Nitrosamine-induced Rat Bladder Carcinogenesis / 대한비뇨기과학회지

ABSTRACT

PURPOSE: To determine the role of TGF-beta1, and its receptors, in bladder tumor, their expressions at various stages of chemically-induced rat bladder carcinogenesis were investigated. MATERIALS AND METHODS: Forty female Sprague-Dawley rats (200-250g) were given drinking water containing 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), and twenty rats, used as a control group, were given tap water. After 10, 20, 25 and 30 weeks of the administration, the bladders of the rats were harvested. The control and BBN-treated rat bladders were analyzed for the expressions of TGF-beta1, and its receptors (RI, RII and RIII), in the mRNA by a real-time quantitative polymerase chain reaction. The protein expression was determined by immunohistochemistry. RESULTS: The expressions of the TGF-beta1 increased in the mRNA with the BBN treatment, while those of the TGF-beta receptors decreased. The up-regulation of TGF-beta1 was statistically significant after 25 weeks of BBN treatment, but down-regulations of RI, RII, and RIII were significant after 20, 25, and 30 weeks of BBN treatment, respectively (p<0.05). The immunohistochemical analysis demonstrated that the TGF-beta1, and its receptors, were localized in the tumor cytoplasm, and their intensities reflected the expression in the mRNA of these tissues. CONCLUSIONS: These data suggest that the enhanced expression of TGF-beta1, as well as the loss of the expressions of RI, RII, and RIII, at the various stages, contributes to the carcinogenesis of the bladder and tumor progression.