MANGANESE SUPEROXIDE-DISMUTASE EXPRESSION INHIBITS SOFT AGAR GROWTH IN JB6 CLONE41 MOUSE EPIDERMAL-CELLS

Manganese superoxide dismutase (MnSOD) has been found to be depleted i n a variety of tumor cells as well as in in vitro transformed cell lin es, suggesting that MnSOD may function as an anticarcinogen by protect ing the cell from oxidant-induced carcinogenesis, The relationship bet ween MnSOD expression and tumor promotion was studied by transfection of a human MnSOD cDNA into the promotable mouse epidermal cell line JB 6 clone41, The effect of MnSOD overexpression on the promotion-sensiti ve phenotype of JB6 cells was assessed by measuring growth characteris tics such as growth rate and the ability to form colonies in soft agar . Compared with the parental and vector-transfected (gpt) control cell s, MnSOD-overexpressing cells had a slower growth rate and their abili ty to form colonies in soft agar was significantly decreased in respon se 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 compare d 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-sensi tive phenotype of JB6 clone41 cells can be reverted by increasing MnSO D intracellularly. A possible mechanism is that elevated MnSOD express ion might change the intracellular redox state by altering the balance of reactive oxygen species, This could lead to a modulation of TPA an d oxidant-induced signal transduction pathways controlling cell growth and differentiation.