SOD2: A new type of tumor‐suppressor gene?

Abstract

The activity of superoxide dismutases (SOD) 1 and 2 was analysed in correlation with mRNA and chromosome content in 6 SV40-transformed (TF) and in non-transformed (NF) human fibroblast cell lines. Total SOD activity was fairly constant, whereas the ratio SOD2/SOD1 was much lower in TF than in NF. The decrease in SOD2 activity was correlated with a low mRNA content, and with the presence of various chromosomal rearrangements leading to deletions of the long arm of chromosome 6 where the gene is mapped. In contrast, chromosome 21, carrying the gene for SOD1, was not found to be deficient and the SOD1 activity was high. This shows that in TF, the activity of SOD2 is largely determined by gene dosage. It has been proposed that SOD activity could be inversely correlated with cell proliferation, and that SOD2 activity, in particular, was related to cell differentiation. Thus, there is a cascade of events occurring in cell transformation, involving gene deregulation, chromosome (gene) deletion, low mRNA and protein content, low enzyme activity, and acquisition of growth advantage which makes the SOD2 gene a possible new type of tumor-suppressor gene.

Upregulation of manganese superoxide dismutase (SOD2) is a common pathway for neuroendocrine differentiation in prostate cancer cells

“…Bravard and colleagues first proposed MnSOD as a potential tumor suppressor gene that might also be involved in differentiation. 25 First evidences came from studies in immortal rat embryo fibroblasts that undergo spontaneous differentiation into muscle and adipose cells, process that is accompanied with a significant increase in MnSOD activity. 30 This phenomenon can be extended to some fungi in which MnSOD expression is also associated with both oval and falcate conidia differentiation.…”

“…25 Given that melatonin is an antioxidant agent either as a direct scavenger or indirectly by modulating the expression of antioxidant enzymes or glutathione content, 26 we decided to study the levels of MnSOD in melatonininduced NE-differentiated cells and compared with control, nondifferentiated cells. MnSOD but not CuZnSOD immunoreactivity increased in NE-like differentiated cells, either with MEL, cs-FBS or with db-cAMP (Fig.…”

Epigenetic Regulation of Manganese Superoxide Dismutase Expression in Human Breast Cancer Cells

“…[5][6][7] Collectively, these findings have led to the hypothesis that that MnSOD functions as a type of tumor suppressor gene. 8 Breast carcinoma cells and primary tumors generally have lower MnSOD expression and activity than their normal nontumorgenic counterparts. 3 However, the precise mechanism leading to the down regulation of MnSOD during malignant transformation is unclear.…”

Manganese superoxide dismutase suppresses hypoxic induction of hypoxia-inducible factor-1α and vascular endothelial growth factor

“…It has been shown that the malignant phenotype is suppressed when MnSOD activity is elevated in certain cancer cells (Li et al, 1998a, b;Zhang et al, 1999). MnSOD has been implicated as a tumor suppressor and as a metastasis suppressor in some tumor cell lines (Oberley and Buettner, 1979;Oberley and Oberley, 1988;Bravard et al, 1992). MnSOD modulates the cellular redox environment by converting superoxide radical (O 2 À ) to H 2 O 2 and dioxygen.…”