Abstract 2727: Sulfiredoxin is required for AOM/DSS induced mouse colon carcinogenesis and invasiveness of human colon cancer cells.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Sulfiredoxin (Srx) is the enzyme that reduces the overoxidized inactive form of peroxiredoxins (Prxs). To study the function of Srx in carcinogenesis in vivo, we tested whether loss of Srx protects mice from cancer development. Srx null mice were generated and colon carcinogenesis was induced by an azoxymethane (AOM) and dextran sulfate sodium (DSS) protocol. Compared to either wildtype or heterozygotes, Srx-/- mice had significantly reduced rates in both tumor multiplicity and volume. Mechanistic studies reveal that loss of Srx did not alter tumor cell proliferation; however, increased apoptosis and decreased inflammatory cell infiltration were obvious in tumors from Srx null mice compared to those from wildtype control. In addition to the AOM/DSS model, examination of Srx expression in human reveals a tissue-specific expression pattern. Srx expression was also demonstrated in tumors from colorectal cancer patients and the levels of expression were associated with patients’ clinic stage. These data provide the first in vivo evidence that loss of Srx renders mice resistance to AOM/DSS-induced colon carcinogenesis, suggesting that Srx has a critical oncogenic role in cancer development, and Srx may be used as a marker for human colon cancer pathogenicity. Citation Format: Qiou Wei, Hong Jiang, Alyson Baker, Lisa K. Dodge, Matthieu Gerard, Matthew R. Young, Michel B. Toledano, Nancy H. Colburn. Sulfiredoxin is required for AOM/DSS induced mouse colon carcinogenesis and invasiveness of human colon cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2727. doi:10.1158/1538-7445.AM2013-2727 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.