title: Inherited cancer predisposition sensitizes colonic mucosa to address Western diet effects and putative cancer-predisposing changes on mouse proteome.
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.
authors.affiliation: Department of Biosciences, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Denis
authors.initials: D
authors.lastname: Đermadi
authors.affiliation: Department of Biosciences, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Valo
authors.affiliation: Department of Biosciences, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Marjaana
authors.initials: M
authors.lastname: Pussila
authors.affiliation: Department of Information and Computer Science, School of Science, Aalto University, FI-00076 Espoo, Finland.
authors.forename: Nima
authors.initials: N
authors.lastname: Reyhani
authors.affiliation: Department of Biosciences, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Sarantaus
authors.affiliation: Meilahti Clinical Proteomics Core Facility, Biochemistry and Developmental Biology, Institute of Biomedicine, University of Helsinki, FI-00014 Helsinki, Finland; Folkhälsan Institute of Genetics, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Lalowski
authors.affiliation: Meilahti Clinical Proteomics Core Facility, Biochemistry and Developmental Biology, Institute of Biomedicine, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Marc
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Department of Biosciences, University of Helsinki, FI-00014 Helsinki, Finland. Electronic address: minna.nystrom@helsinki.fi.
authors.forename: Minna
authors.initials: M
authors.lastname: Nyström
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D005227:Fatty Acids / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000008:administration & dosage; D007413:Intestinal Mucosa / Q000473:pathology*; D051379:Mice; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D020543:Proteome; D015430:Weight Gain
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005227:Fatty Acids; C501485:Mlh1 protein, mouse; D009687:Nuclear Proteins; D020543:Proteome; D000070957:MutL Protein Homolog 1; D005947:Glucose
keywords: 2D DIGE; Colorectal cancer; Lynch syndrome; MLH1; Proteomics; Western diet