Manganese superoxide dismutase deficiency enhances cell turnover via tumor promoter-induced alterations in AP-1 and p53-mediated pathways in a skin cancer model.

Previous studies in our laboratories demonstrated that overexpression of manganese superoxide dismutase (MnSOD) suppressed both the incidence and multiplicity of papillomas in a DMBA/TPA multi-stage skin carcinogenesis model. The activity of activator protein-1 (AP-1), which is associated with tumor promotion, was reduced in MnSOD transgenic mice overexpressing MnSOD in the skin, suggesting that MnSOD may reduce tumor incidence by suppressing AP-1 activation. In the present study, we report that reduction of MnSOD by heterozygous knockout of the MnSOD gene (Sod2 -/+, MnSOD KO) increased the levels of oxidative damage proteins and the activity of AP-1 following TPA treatment.