OVEREXPRESSION OF CYCLIN-D1 AND CYCLIN-E IN N-NITROSOMETHYLBENZYLAMINE-INDUCED RAT ESOPHAGEAL TUMORIGENESIS

Dysregulation of G1 cyclins has been implicated in several human malig nancies, To further investigate the role of G1 cyclins in chemical car cinogenesis, 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 esoph ageal epithelium. Cyclin E mRNA levels were increased 6.2-fold in 25 w eek (P < 0.01) and 6.9-fold in 45 week (P < 0.01) papillomas. Immunohi stochemical staining revealed exclusive nuclear staining of both cycli n D1 and cyclin E, Furthermore, there was a sequential increase in cyc lin D1- and cyclin E-positive cells from normal epithelium, to preneop lastic lesions, to papillomas. These findings suggest that overexpress ion of cyclin D1 and cyclin E occur relatively early in rat esophageal tumorigenesis and participate in tumor progression in this model.