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

Dysregulation of G1 cyclins has been implicated in several human malignancies. To further investigate the role of G1 cyclins in chemical carcinogenesis, the expression of cyclin D1 and cyclin E was analyzed by RT-PCR and immunohistochemical studies in N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. Cyclin D1 mRNA levels were increased 2.8-fold in 25 week (P < 0.05) and 6.8-fold in 45 week (P < 0.01) papillomas induced by NMBA, when compared with normal rat esophageal epithelium. Cyclin E mRNA levels were increased 6.2-fold in 25 week (P < 0.01) and 6.9-fold in 45 week (P < 0.01) papillomas. Immunohistochemical staining revealed exclusive nuclear staining of both cyclin D1 and cyclin E. Furthermore, there was a sequential increase in cyclin D1- and cyclin E-positive cells from normal epithelium, to preneoplastic lesions, to papillomas. These findings suggest that overexpression of cyclin D1 and cyclin E occur relatively early in rat esophageal tumorigenesis and participate in tumor progression in this model.