title: Loss of sulfiredoxin renders mice resistant to azoxymethane/dextran sulfate sodium-induced colon carcinogenesis.
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 wild-type (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.
authors: Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA. qiou.wei@uky.edu
authors: Qiou
authors: Q
authors: Wei
authors: Hong
authors: H
authors: Jiang
authors: Alyson
authors: A
authors: Baker
authors: Lisa K
authors: LK
authors: Dodge
authors: Matthieu
authors: M
authors: Gerard
authors: Matthew R
authors: MR
authors: Young
authors: Michel B
authors: MB
authors: Toledano
authors: Nancy H
authors: NH
authors: Colburn
mesh_terms: D000818:Animals; D017209:Apoptosis; D001397:Azoxymethane; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D016264:Dextran Sulfate; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins / Q000378:metabolism
chemical_list: D016264:Dextran Sulfate; D054464:Peroxiredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C529381:sulfiredoxin protein, mouse; C504024:SRXN1 protein, human; D001397:Azoxymethane
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