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Author (up) Polakova Vymetalkova, V.; Vannucci, L.; Korenkova, V.; Prochazka, P.; Slyskova, J.; Vodickova, L.; Rusnakova, V.; Bielik, L.; Burocziova, M.; Rossmann, P.; Vodicka, P.
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  Title Evaluation of tumor suppressor gene expressions and aberrant methylation in the colon of cancer-induced rats: a pilot study Type Journal Article
  Year 2013 Publication Molecular Biology Reports Abbreviated Journal Mol Biol Rep  
  Volume Issue Pages  
  Abstract Altered expression and methylation pattern of tumor suppressor and DNA repair genes, in particular involved in mismatch repair (MMR) pathway, frequently occur in primary colorectal (CRC) tumors. However, little is known about (epi)genetic changes of these genes in precancerous and early stages of CRC. The aim of this pilot study was to analyze expression profile and promoter methylation status of important tumor suppressor and DNA repair genes in the early stages of experimentally induced colorectal carcinogenesis. Rats were treated with azoxymethane (AOM), dextran sodium sulphate (DSS) or with their combination, and sacrificed 1 or 4 months post-treatment period. The down-regulation of Apc expression in left colon, detectable in animals treated with DSS-AOM and sacrificed 1 month after the end of treatment, represents most early marker of the experimental colorectal carcinogenesis. Significantly reduced gene expressions were also found in 5 out of 7 studied MMR genes (Mlh1, Mlh3, Msh3 Pms1, Pms2), regarding the sequential administration of DSS-AOM at 4 months since the treatment. Strong down-regulation was also discovered for Apc, Apex1, Mgmt and TP53. Tumors developed in rectum-sigmoid region displayed significantly lower Apc and Pms2 expressions. The decreased expression of studied genes was not in any case associated with aberrant methylation of promoter region. Present data suggest that down-regulation of Apc and MMR genes are prerequisite for the development of CRC. In this study we addressed for the first time early functional alterations of tumor suppressor genes with underlying epigenetic mechanisms in experimentally induced CRC in rats.  
  Address Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14200, Prague 4, Czech Republic  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0301-4851 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24065530 Approved no  
  Call Number @ @ Serial 42511  
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