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

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.