Abstract 4389: Potential role of superoxide dismutase 3 in prevention of estrogen-induced breast cancer

Abstract

Abstract Estrogens have been implicated in the development of human breast cancers. Literature and our studies strongly support the role of oxidative stress in estrogen-induced breast carcinogenesis. We have recently demonstrated for the first time that antioxidants vitamin C or butylated hydroxyanisole (BHA) attenuate 17β-estradiol (E2)-induced oxidative stress; increase the latency of tumor development; and, severely inhibit E2-induced breast tumor development in female ACI rats. The female ACI rat is an established animal model to study the mechanisms of E2-induced breast cancer. The objective of the present study was to identify genes that may provide an insight into the mechanism of inhibition of E2-induced breast carcinogenesis by vitamin C or BHA. Microarray analyses were performed on total RNA isolated from breast and breast tumor tissues of rats treated with E2 (3 mg, s.c.); vitamin C (1% in drinking water); BHA (0.7% in diet); vitamin C + E2 and BHA + E2 for 8 months. A number of genes were shown to be differentially expressed in breast tissue and tumor tissue of rats treated with E2 vs. other treatments. One gene of interest identified was extracellular superoxide dismutase (SOD3) that was 18-fold suppressed in mammary tumors vs. normal mammary tissue and more than 6-fold decreased in mammary tissue of E2 treated animals vs. normal age-matched controls. Protein expression data confirmed the suppression of SOD3 in mammary tissue of E2-treated rats and in mammary tumors. This suppression was overcome by co-treatment of rats with E2 and vitamin C or BHA. SOD3 was induced 2.9- and 2.1-fold respectively by treatments of rats with vitamin C or BHA compared to sham-treated controls. SOD3 expression was not regulated by vitamin C or BHA in the liver tissue suggesting that its expression may be target-organ specific. SOD3 is an extracellular antioxidant enzyme implicated in the prevention of oxidative stress-mediated tissue damage. Thus, SOD3 may play an important role in the prevention of breast cancer and this gene may have a great potential in the development of therapeutic strategies for the prevention of estrogen-induced neoplasia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4389.