Manganese superoxide dismutase (MnSOD) is reduced in a variety of tumor cells and has been proposed to be a new type of tumor suppressor gene. The mechanism(s) by which MnSOD suppresses cancer development is currently unknown. However, expression of this antioxidant might play a significant role in maintaining cellular redox status. The relationship between MnSOD expression and modulation of DNA-binding activity and transcriptional activation of redox-sensitive oncoproteins and tumor suppressor proteins was studied in a murine fibrosarcoma cell line (FSa-II). Electrophoretic mobility shift assay and transcriptional activation studies revealed an inverse correlation between MnSOD expression and activity of c-jun-associated transcription factors, activator protein 1 and cyclic AMP-responsive element binding protein. Furthermore, expression of an activator protein 1 target gene, bcl-xL, was decreased in MnSOD-transfected cell lines. The results suggest that overexpression of MnSOD may exert its tumor suppressor activity, in part, by modulation of specific oncogenes.
This work was supported by NIH Grants CA 49797 and CA 95835 and Kentucky Tobacco Research Board Grant 5-4113.