Enhancement of erbB2 and erbB3 expression during oral oncogenesis in diabetic rats

Abstract

The expression of erbB2 and erbB3 receptors was investigated in an experimental model of chemically induced oral carcinogenesis in normal and diabetic (type I) Sprague-Dawley rats. Thirteen diabetic and twelve normal rats developed precancerous and cancerous lesions after 4-nitroquinoline-N-oxide treatment, while six diabetic and six normal animals were used as controls. Sections of biopsies from all animals were classified histologically in the following categories: normal mucosa, hyperplasia, dysplasia, early invasion, well- and moderately-differentiated squamous cell carcinoma. Each section was studied immunohistochemically using monoclonal antibodies against erbB2 and erbB3 proteins and six representative histological regions in each section were analysed. The erbB2 was expressed at very low levels in normal rats, while in diabetic animals its expression was significantly increased during early invasion (P = 0.04). The erbB3 expression was significantly elevated in well-differentiated carcinoma in normal animals (P = 0.01), while in diabetic animals it was significantly increased during oral mucosal hyperplasia and dysplasia (P = 0.03 and 0.0007, respectively). The comparison of erbB2 expression between diabetic and normal rats revealed significant differences in all stages except for the tumor stage of moderately differentiated carcinoma (P = 0.01, 0.00001, 0.00001, 0.003, and 0.00001). In regard to erbB3 expression, significant differences between diabetic and normal rats existed only in normal, non-cancerous and precancerous stages (P = 0.007, 0.0001, 0.0003). It seems that diabetes enhances the expression of both erbB2 and erbB3 in certain stages of oral oncogenesis possibly resulting in promotion of cell proliferation and inhibition of apoptosis.