Show simple item record 2016-09-05T14:51:19Z 2016-09-05T14:51:19Z
dc.title Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer es
dc.type Artículo es
dcterms.abstract Molecular mechanisms underlying coordinated hypermethylation of multiple CpG islands in cancer remain unclear and studies of methyltransferase enzymes have arrived at conflicting results. We focused on DNMT1 and DNMT3B, DNA methyltransferases responsible for (de novo) methylation, and EZH2, histone (H3K27) methyltransferase, and examined their roles in tumor suppressor gene (TSG) methylation patterns we have previously established in sporadic and familial cancers. Our investigation comprised 165 tumors, stratified by tissue of origin (117 colorectal and 48 endometrial carcinomas) and sporadic vs. familial disease (57 sporadic vs. 60 familial, mainly Lynch syndrome, colorectal carcinomas). By immunohistochemical evaluation, EZH2 protein expression was associated with a TSG methylator phenotype. DNMT1, DNMT3B, and EZH2 were expressed at significantly higher levels in tumor vs. normal tissues. DNMT1 and EZH2 expression were positively correlated and higher in microsatellite-unstable vs. microsatellite-stable tumors, whether sporadic or hereditary. Ki-67 expression mirrored the same pattern. Promoter methylation of the methyltransferase genes themselves was addressed as a possible cause behind their altered expression. While DNMT1 or EZH2 did not show differential methylation between normal and tumor tissues, DNMT3B analysis corroborated the regulatory role of a distal promoter region. Our study shows that methyltransferase expression in cancer depends on the tissue of origin, microsatellite-instability status, cellular proliferation, and--in the case of DNMT3B--promoter methylation of the respective gene. Translation of methyltransferase expression into DNA methylation appears complex as suggested by the fact that except for EZH2, no clear association between methyltransferase protein expression and TSG methylation was observed. en
dcterms.extent p. 776-787 es
dcterms.issued 2015
dcterms.language Inglés es
dcterms.license Attribution 4.0 International (BY 4.0) es
dcterms.subject Methyltransferase expression en
dcterms.subject tumor suppressor gene methylation en
dcterms.subject colorectal cancer en
cic.version info:eu-repo/semantics/submittedVersion es Pavicic, Walter Hernán es Abdel-Rahman, W. es Peltomäki, P. es Joensuu, E. es Nieminen, T. es Lotsari, J. es
cic.lugarDesarrollo Instituto Multidisciplinario de Biología Celular es
dcterms.subject.materia Ciencias Médicas es
dcterms.isPartOf.issue vol. 54 es
dcterms.isPartOf.series Genes, Chromosomes and Cancer es
cic.isPeerReviewed true es
cic.isFulltext true es


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