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

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 (<i>Selenof</i>) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane...

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Bibliographic Details
Main Authors: Jessica A. Canter, Sarah E. Ernst, Kristin M. Peters, Bradley A. Carlson, Noelle R. J. Thielman, Lara Grysczyk, Precious Udofe, Yunkai Yu, Liang Cao, Cindy D. Davis, Vadim N. Gladyshev, Dolph L. Hatfield, Petra A. Tsuji
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/19/10651
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Summary: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 (<i>Selenof</i>) 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 <i>Selenof</i> 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 <i>Selenof</i>’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.
ISSN:1661-6596
1422-0067