Korean J Urol.  2003 Jun;44(6):599-605.

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

• Ryu SB
• Oh KJ
• Kwon DD
• Oh BR
• Kim SY
• Choi IS
• Choi C

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.

Keyword

Bladder neoplasms; Transforming growth factor beta1; Receptors; transforming growth factor beta; Butyl hydroxybutyl nitrosamine

MeSH Terms

Animals
Carcinogenesis*
Cytoplasm
Drinking Water
Female
Humans
Immunohistochemistry
Polymerase Chain Reaction
Rats*
Rats, Sprague-Dawley
Receptors, Transforming Growth Factor beta
RNA, Messenger
Transforming Growth Factor beta
Transforming Growth Factor beta1
Up-Regulation
Urinary Bladder Neoplasms
Urinary Bladder*
Water
Drinking Water
RNA, Messenger
Receptors, Transforming Growth Factor beta
Transforming Growth Factor beta
Transforming Growth Factor beta1
Water