Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Aberrant Crypt Foci/*diet therapy ; Aberrant Crypt Foci/*metabolism ; Carcinogenesis/*drug effects ; Colonic Neoplasms/*blood ; Colonic Neoplasms/*diet therapy ; Intestinal Mucosa/*metabolism ; Selenoproteins/*metabolism ; Sodium Selenite/*administration & dosage ; Trace Elements/*administration & dosage; Aberrant Crypt Foci/genetics ; Animals ; Azoxymethane/adverse effects ; Carcinogenesis/genetics ; Colonic Neoplasms/chemically induced ; Colonic Neoplasms/genetics ; Cytokines/blood ; Dextran Sulfate/adverse effects ; Diet/methods ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic/drug effects ; Intestinal Mucosa/drug effects ; Male ; Mice ; Mice, Knockout ; Selenoproteins/genetics ; Signal Transduction/drug effects ; Signal Transduction/genetics
    • Abstract:
      Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein ( Selenof ) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof 's potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.
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    • Grant Information:
      R01 AG021518 United States AG NIA NIH HHS; R01 GM061603 United States GM NIGMS NIH HHS
    • Contributed Indexing:
      Keywords: Selenof; barrier integrity; colon cancer; inflammation; selenium; selenoprotein
    • Accession Number:
      0 (Cytokines)
      0 (Selenof protein, mouse)
      0 (Selenoproteins)
      0 (Trace Elements)
      9042-14-2 (Dextran Sulfate)
      HIW548RQ3W (Sodium Selenite)
      MO0N1J0SEN (Azoxymethane)
    • Publication Date:
      Date Created: 20211013 Date Completed: 20211108 Latest Revision: 20240513
    • Publication Date:
      20240513
    • Accession Number:
      PMC8508755
    • Accession Number:
      10.3390/ijms221910651
    • Accession Number:
      34638991