Knockout of the 15 kDa Selenoprotein Protects against Chemically-Induced Aberrant Crypt Formation in Mice

Petra A. Tsuji, Bradley A. Carlson, Salvador Naranjo-Suarez, Min Hyuk Yoo, Xue Ming Xu, Dmitri E. Fomenko, Vadim N. Gladyshev, Dolph L. Hatfield, Cindy D. Davis

Research output: Contribution to journalArticle

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Abstract

Evidence suggests that selenium has cancer preventive properties that are largely mediated through selenoproteins. Our previous observations demonstrated that targeted down-regulation of the 15 kDa selenoprotein (Sep15) in murine colon cancer cells resulted in the reversal of the cancer phenotype. The present study investigated the effect of Sep15 knockout in mice using a chemically-induced colon cancer model. Homozygous Sep15 knockout mice, and wild type littermate controls were given four weekly subcutaneous injections of azoxymethane (10 mg/kg). Sep15 knockout mice developed significantly (p<0.001) fewer aberrant crypt foci than controls demonstrating that loss of Sep15 protects against aberrant crypt foci formation. Dietary selenium above adequate levels did not significantly affect aberrant crypt foci formation in Sep15 knockout mice. To investigate molecular targets affected by loss of Sep15, gene expression patterns in colonic mucosal cells of knockout and wild type mice were examined using microarray analysis. Subsequent analyses verified that guanylate binding protein-1 (GBP-1) mRNA and protein expression were strongly upregulated in Sep15 knockout mice. GBP-1, which is expressed in response to interferon-γ, is considered to be an activation marker during inflammatory diseases, and up-regulation of GBP-1 in humans has been associated with a highly significant, increased five-year survival rate in colorectal cancer patients. In agreement with these studies, we observed a higher level of interferon-γ in plasma of Sep15 knockout mice. Overall, our results demonstrate for the first time, that Sep15 knockout mice are protected against chemically-induced aberrant crypt foci formation and that Sep15 appears to have oncogenic properties in colon carcinogenesis in vivo.

Original languageEnglish (US)
Article numbere50574
JournalPloS one
Volume7
Issue number12
DOIs
StatePublished - Dec 4 2012

Fingerprint

Selenoproteins
selenoproteins
Knockout Mice
Carrier Proteins
Aberrant Crypt Foci
Selenium
Interferons
mice
Azoxymethane
Microarrays
colorectal neoplasms
Gene expression
binding proteins
Chemical activation
Cells
interferons
Colonic Neoplasms
Plasmas
Messenger RNA
selenium

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Tsuji, P. A., Carlson, B. A., Naranjo-Suarez, S., Yoo, M. H., Xu, X. M., Fomenko, D. E., ... Davis, C. D. (2012). Knockout of the 15 kDa Selenoprotein Protects against Chemically-Induced Aberrant Crypt Formation in Mice. PloS one, 7(12), [e50574]. https://doi.org/10.1371/journal.pone.0050574

Knockout of the 15 kDa Selenoprotein Protects against Chemically-Induced Aberrant Crypt Formation in Mice. / Tsuji, Petra A.; Carlson, Bradley A.; Naranjo-Suarez, Salvador; Yoo, Min Hyuk; Xu, Xue Ming; Fomenko, Dmitri E.; Gladyshev, Vadim N.; Hatfield, Dolph L.; Davis, Cindy D.

In: PloS one, Vol. 7, No. 12, e50574, 04.12.2012.

Research output: Contribution to journalArticle

Tsuji, PA, Carlson, BA, Naranjo-Suarez, S, Yoo, MH, Xu, XM, Fomenko, DE, Gladyshev, VN, Hatfield, DL & Davis, CD 2012, 'Knockout of the 15 kDa Selenoprotein Protects against Chemically-Induced Aberrant Crypt Formation in Mice', PloS one, vol. 7, no. 12, e50574. https://doi.org/10.1371/journal.pone.0050574
Tsuji, Petra A. ; Carlson, Bradley A. ; Naranjo-Suarez, Salvador ; Yoo, Min Hyuk ; Xu, Xue Ming ; Fomenko, Dmitri E. ; Gladyshev, Vadim N. ; Hatfield, Dolph L. ; Davis, Cindy D. / Knockout of the 15 kDa Selenoprotein Protects against Chemically-Induced Aberrant Crypt Formation in Mice. In: PloS one. 2012 ; Vol. 7, No. 12.
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