Inherited cancer predisposition sensitizes colonic mucosa to address Western diet effects and putative cancer-predisposing changes on mouse proteome

Denis Dermadi Bebek, Satu Valo, Marjaana Pussila, Nima Reyhani, Laura Sarantaus, Maciej Lalowski, Marc Baumann, Minna Nyström*

*Corresponding author for this work

    Research output: Contribution to journalArticleScientificpeer-review

    4 Citations (Scopus)

    Abstract

    Human epidemiological evidence and previous studies on mice have shown that Western-style diet (WD) may predispose gut mucosa to colorectal cancer (CRC). The mechanisms that mediate the effects of diet on tumorigenesis are largely unknown. To address putative cancer-predisposing events available for early detection, we quantitatively analyzed the proteome of histologically normal colon of a wild-type (Mlh1+/+) and an Mlh1+/- mouse after a long-term feeding experiment with WD and AIN-93G control diet. The Mlh1+/- mouse carries susceptibility to colon cancer analogous to a human CRC syndrome (Lynch syndrome). Remarkably, WD induced expression changes reflecting metabolic disturbances especially in the cancer-predisposed colon, while similar changes were not significant in the wild-type proteome. Overall, the detected changes constitute a complex interaction network of proteins involved in ATP synthesis coupled proton transport, oxidoreduction coenzyme and nicotinamide nucleotide metabolic processes, important in cell protection against reactive oxygen species toxicity. Of these proteins, selenium binding protein 1 and galectin-4, which directly interact with MutL homolog 1, are underlined in neoplastic processes, suggesting that sensitivity to WD is increased by an Mlh1 mutation. The significance of WD on CRC risk is highlighted by the fact that five out of six mice with neoplasias were fed with WD.

    Original languageEnglish
    Pages (from-to)1196-1206
    Number of pages11
    JournalJOURNAL OF NUTRITIONAL BIOCHEMISTRY
    Volume25
    Issue number11
    DOIs
    Publication statusPublished - 1 Nov 2014
    MoE publication typeA1 Journal article-refereed

    Keywords

    • 2D DIGE
    • Colorectal cancer
    • Lynch syndrome
    • MLH1
    • Proteomics
    • Western diet

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