LAUSR

Mitochondrial superoxide dismutase (SOD2/MnSOD) is a primary line of antioxidant defense. Under aerobic conditions, its role detoxifying superoxide into H2O2 is crucial, as deduced from the early death of SOD2-/- KO mice after birth. SOD2 has been reported as a key enzyme that increases along with tumor progression in the prostate. To get a further insight into the role of SOD2 in tumor progression, we crossbred transgenic prostate cancer mice (TRAMP) with either SOD2+/- or SOD2+/++ mice. TRAMPSOD2+/-showed a similar tumor growth and survival rate compared to TRAMP mice, thus demonstrating that a roughly 50% reduction in SOD2 expression and/or activity is not enough to cause a dramatic change in tumor progression. On the contrary, TRAMPSOD2+/++, which display a systemic overexpression of SOD2, show an increased tumor growth rate and a much poorer prognosis. Castration initially prevents tumor growth and relapses are rarely observed before 50 weeks of age in TRAMP mice. Interestingly, castrated TRAMPSOD+/++ display poorly differentiated tumors early in life (24 wk.), mostly with a neuroendocrine profile, and a short life expectancy compared to TRAMP mice. Finally, differences in AR expression/activity and metastatic parameters were also determined in all the experimental groups.