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

Abstract

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.