Manganese superoxide dismutase expression inhibits soft agar growth in JB6 clone41 mouse epidermal cells.
Manganese superoxide dismutase (MnSOD) has been found to be depleted in a variety of tumor cells as well as in in vitro transformed cell lines, suggesting that MnSOD may function as an anticarcinogen by protecting the cell from oxidant-induced carcinogenesis. The relationship between MnSOD expression and tumor promotion was studied by transfection of a human MnSOD cDNA into the promotable mouse epidermal cell line JB6 clone41. The effect of MnSOD overexpression on the promotion-sensitive phenotype of JB6 cells was assessed by measuring growth characteristics such as growth rate and the ability to form colonies in soft agar. Compared with the parental and vector-transfected (gpt) control cells, MnSOD-overexpressing cells had a slower growth rate and their ability to form colonies in soft agar was significantly decreased in response to 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. Since the transformation-sensitive phenotype of JB6 clone41 cells is associated with increased expression of the transcription factor AP-1, we compared c-jun and c-fos mRNA expression in MnSOD-transfected and control JB6 cells. Overexpression of MnSOD led to a significant decrease in c-jun and c-fos expression in response to treatment with TPA or the oxidant promoter superoxide. These findings indicate that the promotion-sensitive phenotype of JB6 clone41 cells can be reverted by increasing MnSOD intracellularly. A possible mechanism is that elevated MnSOD expression might change the intracellular redox state by altering the balance of reactive oxygen species. This could lead to a modulation of TPA and oxidant-induced signal transduction pathways controlling cell growth and differentiation.
Amstad
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PA
Department of Pathology, University of Maryland, Baltimore 21201, USA.
Liu
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Ichimiya
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M
Berezesky
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IK
Trump
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D000818:Animals; D002273:Carcinogens; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D004198:Disease Susceptibility; D004790:Enzyme Induction; D000078404:Epidermal Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D051379:Mice; D018384:Oxidative Stress; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D002273:Carcinogens; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate