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Sep15 knockout in mice provides protection against chemically‐induced aberrant crypt formation
Author(s) -
Tsuji Petra A,
Carlson Bradley A,
Yoo MinHyuk,
Xu XueMing,
NaranjoSuarez Salvador,
Fomenko Dmitri,
Hatfield Dolph L,
Gladyshev Vadim N,
Davis Cindy D
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.110.1
Subject(s) - azoxymethane , aberrant crypt foci , knockout mouse , microbiology and biotechnology , selenoprotein , biology , carcinogen , cancer , biochemistry , gene , carcinogenesis , superoxide dismutase , colorectal cancer , oxidative stress , glutathione peroxidase , genetics , colonic disease
The essential nutrient selenium appears to have cancer preventive properties that are partly mediated through selenoproteins. This study investigated the role of the 15 kDa selenoprotein (Sep15) in cancer by examining Sep15 knockout (k.o.) in mice. Weanling homozygous Sep15 k.o., heterozygote and wild type littermate controls (N=12/genotype) were given four weekly subcutaneous injections of the colon carcinogen azoxymethane (10 mg/kg). Sep15 k.o. mice developed significantly (p<0.001) fewer aberrant crypt foci (ACF) than controls. Dietary selenium (0, 0.1 or 2.0 ug selenium/g diet) did not significantly affect ACF formation in Sep15 k.o. mice. To investigate molecular targets affected by Sep15 k.o., gene expression patterns in colonic mucosal cells of k.o. and wild type mice were compared with microarrays and Ingenuity Pathway Analysis. Quantitative PCR and western blot analysis revealed guanylate binding protein‐1 (GBP1) mRNA and protein expression to be strongly upregulated in Sep15 k.o. mice. Furthermore, serum analysis indicated significant differences in cytokine expression in Sep15 k.o. mice. Our results suggest that Sep15 k.o. mice are protected against chemically‐induced ACF formation possibly through alterations in inflammatory pathways. Funded by NCI Intramural support, the Cancer Prevention Fellowship Program, NIH grants and the Division of Cancer Prevention.