P 142 - TRAMP mice overexpressing SOD2 develop poorly differentiated neuroendocrine tumors and lower survival

Abstract

In addition of being a primary defense against O 2 •– SOD2, the mitochondrial antioxidant enzyme was claimed for years to have a tumor suppressor role. However, in the last few years numerous reports indicate that, rather on the contrary this enzyme is associated with poor patient outcome and a more aggressive disease in a wide variety of tumors. We used murine model C57BL/6-Tg (TRAMP) 8247Ng/J as well as Sod2+/- knockdown and Sod2+/++ overexpressing mice to generate 2 additional phenotypes TRAMP/Sod2+/- and TRAMP/Sod2+/++ to study the influence of systemic modification of expression levels of SOD2 in prostate cancer. We studied the tumor progression at different ages analyzing genitourinary system weight, tumor diagnosis, androgen receptor (AR), BCL-2, matrix metalloproteinases (MMPs), VEGF and redox enzymes levels. We found that an overexpression of SOD2 not only brought a more malignant tumor diagnosis (mostly poorly differentiated) but also compromised the survival of these mice. Moreover, castration at 12 weeks of age of the three phenotypes showed that TRAMP/Sod2+/++ mice had a relapse rate dramatically higher. These mice mostly developed poorly differentiated neuroendocrine tumors with multiple metastasis, and its survival rate was very low.