Overexpression of cyclin D1 and cyclin E in N-nitrosomethylbezylamine-induced rat esophageal tumorigenesis

Dysregulation of Gl cyclins has been implicated in several humanmalignancies. To further investigate the role of Gl cyclinsin chemical carcinogenesis, the expression of cyclin Dl andcyclin E was analyzed by RT-PCR and immunohistochemical studiesin N-nitrosomethylbenzylamine (NMBA)-induced rat esophagealtumongenesis. Cyclin Dl mRNA levels were increased 2.8-foldin 25 week (P < 0.05) and 6.8-fold in 45 week (P < 0.01)papillomas induced by NMBA, when compared with normal rat esophagealepithelium. Cyclin E mRNA levels were increased 6.2-fold in25 week (P < 0.01) and 6.9-fold in 45 week (P < 0.01)papillomas. Immunohistochemical staining revealed exclusivenuclear staining of both cyclin Dl and cyclin E. Furthermore,there was a sequential increase in cyclin Dl and cyclin E-positivecells from normal epithelium, to preneoplastic lesions, to papillomas.These findings suggest that overexpression of cyclin Dl andcyclin E occur relatively early in rat esophageal tumongenesisand participate in tumor progression in this model.