Journal
PROTEOMICS
Volume 14, Issue 21-22, Pages 2558-2565Publisher
WILEY
DOI: 10.1002/pmic.201400280
Keywords
Animal proteomics; Carcinogenesis; Colorectal cancer; Folate-deficient diet; MTHFR; NuRD complex
Funding
- Canadian Institutes of Health Research [MOP 77596]
- Fonds de recherche du Quebec-Sante [24498]
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Colorectal cancer risk is increased when dietary folate intake is low, with or without a deficiency in methylenetetrahydrofolate reductase (MTHFR). We have observed that intestinal tumors are induced in mice fed low-folate diets, and that tumor incidence is increased when these mice also have MTHFR deficiency. This study was undertaken to identify differentially expressed proteins in conditions favoring initial steps of murine carcinogenesis in normal preneoplastic intestine. We compared the proteome of BALB/c normal intestine in Mthfr(+/+) mice fed control diets for 1 year (low susceptibility to tumorigenesis) with the proteome of Mthfr(+/-) animals fed low folate diets (higher tumor susceptibility). Our data suggest that the NuRD complex, KRAS-related proteins, the protein synthetic machinery, and fatty acid-related metabolic proteins are upregulated in the early stages of tumorigenesis. These proteins may serve as biomarkers or targets for colorectal cancer diagnosis or therapy.
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