N-butyl-N(4-hydroxybutyl) Nitrosamine에 의한 흰쥐방광암 발생과정에서 E-cadherin과 Catenin의 발현

Abstract

Although urothelial cell carcinoma is the most common primary tumor of the urinary bladder, the mechanisms that regulate its development and progression remain unclear. β-catenin plays a fundamental role in the regulation of E-cadherin-catenin cell adhesion complex. Mutations in either β-catenin or E-cadherin gene result in up or down-regulation of protein expression. This study was conducted to evaluate the expression changes of β-catenin and E-cadherin protein during 0.05% BBN-induced rat bladder carcinogenesis. Spray-Dawley Rats were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) by drinking water, and sacrificed at 5, 10, 20, and 30 weeks following treatment. For sequential changes and the expression of E-cadherin and β-catenin during rat bladder tumorigenesis, morphologic assesment and immunohistochemical staining were done. During the carcinogenesis, sequential histological changes from hyperplasia to papilloma, and ultimately overt carcinomas were noted. On histopathological findings, urothelial cell hyperplasias was appeared at 5 weeks, followed by urothelial papillomas at 10 weeks, and superficial urothelial carcinomas was found at 20 weeks after BBN administration. After 30 weeks of BBN administration, invasive carcinomas were developed. The immunohistochemical stains for E-cadherin and β-catenin displayed reduced expression in papilloma and carcinomas. Abnormal cytoplasmic expression of E-cadherin and β-catenin were observed in papillomas and carcinoms, especially in invasive carcinomas. In summary, the loss or reduced expression of E-cadherin and β-catenin are closely related with tumor propagation. Abnormal cytoplasmic expression of E-cadherin and β-catenin are late events favoring tumor progression in superficial type to invasive form in rat BBN-induced bladder cancer. The present study demonstrates that E-cadherin and β-catenin may play an important role in bladder carcinogenesis.