OVEREXPRESSION OF CYCLIN D1 IN RAT ESOPHAGEAL CARCINOGENESIS MODEL

Overexpression of cyclin D1 in human esophageal carcinomas has been we ll documented, The aim of the present study was to assess the expressi on of cyclin D1 in different types of esophageal epithelial lesions in duced by N-nitrosomethylbenzylamine (NMBA) in rats, A total of 30 rats received s.c.-injections, five times/week, of 1.0 mg/kg NMBA for a pe riod of 5 weeks followed by the same dose once per week for another 10 weeks, An additional 15 rats were given saline and used as controls t o provide normal epithelium, The tumor incidence was 100% at the termi nation point of 21 weeks. Seventeen rats (57%) showed nuclear staining for cyclin D1, with a great variation in the intensity, as demonstrat ed by using an immunohistochemical technique, The cyclin D1 positive i ndices were in the range of 0% to 60% of the individual cells. Negligi ble staining was observed for normal esophageal epithelium, with a min imal increase in hyperplastic and dysplastic lesions. A significant el evation of cyclin D1 levels was observed in tumors. However, no signif icant differences were found between papillomas and carcinomas, The im munohistochemical results were confirmed by western blotting analysis, Tumors, papillomas and carcinomas overexpressing cyclin D1 had elevat ed proliferating cell nuclear antigen (PCNA) indices (P <0.05). The co rrelation coefficient of overexpressions of PCNA and cyclin D1 was r=0 .7 for papillomas, but only r=0.3 for carcinomas, The study thus provi des strong evidence of relatively early overexpression of cyclin D1 du ring tumorigenesis in the present rat esophageal model. Cyclin D1 expr ession is not simply a direct consequence of increase cell proliferati on.