These results allow us to reconstruct the sequence of events leading to the decrease of SOD2, a possible tumor-suppressor gene, during the process of SV40-transformation of human fibroblasts.
These results support the hypothesis that increased MnSOD expression suppresses the malignant phenotype of human breast cancer cells and suggests that the MnSOD gene is a tumor suppressor gene in human breast cancer.
These results suggest that levels of MnSOD are highly regulated within C8161 melanoma cells and that SOD2 does not suppress tumor formation nor metastatic potential in all human melanomas.
As a first step in evaluating the tumor suppressor activity of the manganese superoxide dismutase (MnSOD) gene on established tumors in vivo, we used adenovirus-mediated gene transfer as a means of delivering the MnSOD cDNA to hamster cheek pouch carcinoma (HCPC-1) cells in vitro.
In recent studies, decreased expression of Mn SOD, an intramitochondrial enzyme responsible for the dismutation of anion superoxide, has been reported in multiple, malignant cell types, whereas its gene has been proposed as a tumour suppressor gene in melanoma.
In order to understand the molecular mechanism of this anti-tumor effect, we asked whether tumor suppressor gene(s), especially the ones inhibiting tumor invasion and motility, are involved in MnSOD-induced tumor suppression.
These results strengthen the hypothesis that SOD2 has a function as a tumour suppressor gene, but also suggest that the expression of other antioxidant enzymes might be altered in human melanomas.
These results suggest that overexpression of MnSOD gene is involved in the suppression of spontaneous apoptosis, without a resultant alteration in the tumor growth.
Mice with orthotopic thoracic tumors composed of 32D-v-abl cells that received intraesophageal SOD2-PL treatment showed transgenic mRNA in the esophagus at 24 h, but no detectable human SOD2 transgene mRNA in explanted tumors by nested RT-PCR.
Superoxide dismutase-2 (SOD2), which encodes the antioxidant enzyme manganese superoxide dismutase (MnSOD), is a putative tumor suppressor gene whose loss of expression is associated with the malignant phenotype.
Transfection of SOD-2 in M12 cells markedly decreased tumor growth, apoptosis, G1 delay in the cell cycle, and expression of senescence associated beta-galactosidase.
Thus overexpression of human SOD2 in the oral cavity mucosa can prevent radiation-induced mucositis with no detectable compromise in the therapeutic response of orthotopically transplanted tumors.