Overexpression of manganese superoxide dismutase selectively modulates the activity of Jun-associated transcription factors in fibrosarcoma cells.
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.
Kiningham
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KK
Graduate Center for Toxicology, University of Kentucky, Lexington 40536, USA.
St Clair
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DK
D000818:Animals; D002999:Clone Cells; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005354:Fibrosarcoma / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051020:bcl-X Protein; D008156:Luciferases; D013482:Superoxide Dismutase