Diabetes increases both N-ras and ets-1 expression during rat oral oncogenesis resulting in enhanced cell proliferation and metastatic potential.

Background: The expression of N-ras and ets-1 proteins was investigated in an experimental model of chemically- induced carcinogenesis in normal and diabetic (type I) Sprague- Dawley rats. Materials and Methods: Tissue sections ranging from normal mucosa to moderately-differentiated oral squamous cell carcinoma were studied using monoclonal antibodies against N- ras and ets-1 proteins. Results: In diabetic rats, N-ras expression increased with tumor advancement, while in normal rats N-ras was not detected in initial stages of oral oncogenesis and increased only in well-differentiated OSCC. The same pattern of elevated ets-1 expression was observed both in diabetic and normal rats, but in cancerous stages this expression was higher in diabetic than in normal rats. Conclusion: It seems that diabetes may contribute to increased cell proliferation due to N-ras constitutive activation, as well as to enhanced invasion and metastatic potential by increasing ets-1 levels. Oral squamous cell carcinoma (OSCC), including the oral cavity and oropharynx, constitutes the sixth most common cancer worldwide (1). The prognosis for OSCC remains dismal, despite the recent advances in surgery, radiation and chemotherapy, especially if malignant tumors are not diagnosed during the early stages of cancer formation (2). Oral oncogenesis is a multistep process including aberrant expression of oncogenes and tumor suppressor genes leading to the disruption of the normal pathways which control the basic cellular functions, such as cell proliferation and differentiation (3).