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

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Abstract
Dysregulation of Gl cyclins has been implicated in several human malignancies. To further investigate the role of Gl cyclins in chemical carcinogenesis, the expression of cyclin Dl and cyclin E was analyzed by RT-PCR and immunohistochemical studies in N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumongenesis. Cyclin Dl 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 Dl and cyclin E. Furthermore, there was a sequential increase in cyclin Dl and cyclin E-positive cells from normal epithelium, to preneoplastic lesions, to papillomas. These findings suggest that overexpression of cyclin Dl and cyclin E occur relatively early in rat esophageal tumongenesis and participate in tumor progression in this model.

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