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Overexpression of Manganese Superoxide Dismutase Selectively Modulates the Activity of Jun-associated Transcription Factors in Fibrosarcoma Cells¹

Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536

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-x_L, 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.

¹ This work was supported by NIH Grants CA 49797 and CA 95835 and Kentucky Tobacco Research Board Grant 5-4113.

² To whom requests for reprints should be addressed, at the Graduate Center for Toxicology, University of Kentucky, 340 Health Sciences Research Building, Lexington, KY 40536, Phone: (606) 257-3956; Fax: (606) 257-3955.

Received 8/27/97. Accepted 10/16/97.

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