Cancer-Predicting Gene Expression Changes in Colonic Mucosa of Western Diet Fed Mlh1+/- Mice

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dc.contributor Aalto-yliopisto fi
dc.contributor Aalto University en
dc.contributor.author Pussila, Marjaana
dc.contributor.author Sarantaus, Laura
dc.contributor.author Dermadi Bebek, Denis
dc.contributor.author Valo, Satu
dc.contributor.author Reyhani, Nima
dc.contributor.author Ollila, Saara
dc.contributor.author Päivärinta, Essi
dc.contributor.author Peltomäki, Päivi
dc.contributor.author Mutanen, Marja
dc.contributor.author Nyström, Minna
dc.date.accessioned 2017-05-11T09:16:44Z
dc.date.available 2017-05-11T09:16:44Z
dc.date.issued 2013-10-08
dc.identifier.citation Pussila , M , Sarantaus , L , Dermadi Bebek , D , Valo , S , Reyhani , N , Ollila , S , Päivärinta , E , Peltomäki , P , Mutanen , M & Nyström , M 2013 , ' Cancer-Predicting Gene Expression Changes in Colonic Mucosa of Western Diet Fed Mlh1 +/- Mice ' PLOS ONE , vol 8 , no. 10 , e76865 , pp. 1-12 . DOI: 10.1371/journal.pone.0076865 en
dc.identifier.issn 1932-6203
dc.identifier.other PURE UUID: fe95cb0f-d0d0-4f51-84cd-733411c5d8c2
dc.identifier.other PURE ITEMURL: https://research.aalto.fi/en/publications/cancerpredicting-gene-expression-changes-in-colonic-mucosa-of-western-diet-fed-mlh1-mice(fe95cb0f-d0d0-4f51-84cd-733411c5d8c2).html
dc.identifier.other PURE LINK: http://www.scopus.com/inward/record.url?scp=84885127948&partnerID=8YFLogxK
dc.identifier.other PURE FILEURL: https://research.aalto.fi/files/12865620/journal.pone.0076865.pdf
dc.identifier.uri https://aaltodoc.aalto.fi/handle/123456789/25999
dc.description.abstract Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the Western world and interactions between genetic and environmental factors, including diet, are suggested to play a critical role in its etiology. We conducted a long-term feeding experiment in the mouse to address gene expression and methylation changes arising in histologically normal colonic mucosa as putative cancer-predisposing events available for early detection. The expression of 94 growth-regulatory genes previously linked to human CRC was studied at two time points (5 weeks and 12 months of age) in the heterozygote Mlh1+/- mice, an animal model for human Lynch syndrome (LS), and wild type Mlh1+/+ littermates, fed by either Western-style (WD) or AIN-93G control diet. In mice fed with WD, proximal colon mucosa, the predominant site of cancer formation in LS, exhibited a significant expression decrease in tumor suppressor genes, Dkk1, Hoxd1, Slc5a8, and Socs1, the latter two only in the Mlh1+/- mice. Reduced mRNA expression was accompanied by increased promoter methylation of the respective genes. The strongest expression decrease (7.3 fold) together with a significant increase in its promoter methylation was seen in Dkk1, an antagonist of the canonical Wnt signaling pathway. Furthermore, the inactivation of Dkk1 seems to predispose to neoplasias in the proximal colon. This and the fact that Mlh1 which showed only modest methylation was still expressed in both Mlh1+/- and Mlh1+/+ mice indicate that the expression decreases and the inactivation of Dkk1 in particular is a prominent early marker for colon oncogenesis. en
dc.format.extent 1-12
dc.format.mimetype application/pdf
dc.language.iso en en
dc.relation.ispartofseries PLOS ONE en
dc.relation.ispartofseries Volume 8, issue 10 en
dc.rights openAccess en
dc.subject.other Agricultural and Biological Sciences(all) en
dc.subject.other Biochemistry, Genetics and Molecular Biology(all) en
dc.subject.other Medicine(all) en
dc.subject.other 113 Computer and information sciences en
dc.title Cancer-Predicting Gene Expression Changes in Colonic Mucosa of Western Diet Fed Mlh1+/- Mice en
dc.type A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä fi
dc.description.version Peer reviewed en
dc.contributor.department University of Helsinki
dc.contributor.department Tietojenkäsittelytieteen laito
dc.subject.keyword Agricultural and Biological Sciences(all)
dc.subject.keyword Biochemistry, Genetics and Molecular Biology(all)
dc.subject.keyword Medicine(all)
dc.subject.keyword 113 Computer and information sciences
dc.identifier.urn URN:NBN:fi:aalto-201705114374
dc.identifier.doi 10.1371/journal.pone.0076865
dc.type.version publishedVersion


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