Increased growth capacity of cervical-carcinoma cells over-expressing manganous superoxide dismutase

Increases in the expression of manganese-dependent superoxide dismutase (Mn SOD) have been detected in several classes of human and experimental tumors and appear to correlate with poorer prognosis in human neuro-epithelial, o varian and cervical tumors, To delineate the relevance of MnSOD expression to tumor-cell growth and survival, a human MnSOD cDNA was over-expressed in the HeLa cervical-carcinoma cell line. MnSOD over-expression had marginal effects on the growth of HeLa cells in standard medium, but markedly protec ted the cells from growth suppression and cell death in conditions of serum deprivation, Serum starvation did not affect expression of endogenous MnSO D in wild-type HeLa cells, but was associated with increases in cell death and in the generation of intracellular oxygen radicals. By contrast, in HT2 9 colon-carcinoma cells, which are relatively resistant to growth-factor wi thdrawal, serum deprivation was associated with increases in MnSOD expressi on and activity. Together these observations suggest that MnSOD provides a mechanism for counteracting the intracellular oxidative processes that impa ir cell growth and viability in the context of growth-factor withdrawal and , in this context, may promote tumor cell survival in vivo in conditions no rmally unfavorable to cell growth. (C) 1999 Wiley-Liss, Inc.