title: Quantitative proteomics reveals differentially expressed proteins in murine preneoplastic intestine in a model of intestinal tumorigenesis induced by low dietary folate and MTHFR deficiency.
abstract: 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.
authors: Department of Human Genetics, Montreal Children's Hospital, The Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada; Department of Pediatrics, Montreal Children's Hospital, The Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada.
authors: Daniel
authors: D
authors: Leclerc
authors: Kurt
authors: K
authors: Dejgaard
authors: Alexander
authors: A
authors: Mazur
authors: Liyuan
authors: L
authors: Deng
authors: Qing
authors: Q
authors: Wu
authors: Tommy
authors: T
authors: Nilsson
authors: Rima
authors: R
authors: Rozen
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D006712:Homocystinuria / Q000150:complications*; D007413:Intestinal Mucosa / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000473:pathology*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009128:Muscle Spasticity / Q000150:complications*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011618:Psychotic Disorders / Q000150:complications
chemical_list: D020543:Proteome; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Animal proteomics; Carcinogenesis; Colorectal cancer; Folate-deficient diet; MTHFR; NuRD complex