Loss of sulfiredoxin renders mice resistant to azoxymethane/dextran sulfate sodiuminduced colon carcinogenesis

Qiou Wei, Hong Jiang, Alyson Baker, Lisa K. Dodge, Matthieu Gerard, Matthew R. Young, Michel B. Toledano, Nancy H. Colburn

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Sulfiredoxin (Srx) is the enzyme that reduces the hyperoxidized inactive form of peroxiredoxins. 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 with either wildtype (Wt) 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 with those from Wt 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 stages. These data provide the first in vivo evidence that loss of Srx renders mice resistant 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.

Original languageEnglish
Pages (from-to)1403-1410
Number of pages8
JournalCarcinogenesis
Volume34
Issue number6
DOIs
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Cancer Research

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