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      Epigenetic Mechanisms Underlying the Dynamic Expression of Cancer-Testis Genes, PAGE2,-2B and SPANX-B, during Mesenchymal-to-Epithelial Transition

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      Author(s)
      Yilmaz Ozcan, S.
      Sade, A.
      Kucukkaraduman, B.
      Kaygusuz, Y.
      Senses, K. M.
      Banerjee, S.
      Gure, A. O.
      Date
      2014
      Source Title
      PLoS ONE
      Print ISSN
      1932-6203
      Publisher
      pone
      Volume
      9
      Issue
      9
      Pages
      107905-1 - 107905-11
      Language
      English
      Type
      Article
      Item Usage Stats
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      Abstract
      Cancer-testis (CT) genes are expressed in various cancers but not in normal tissues other than in cells of the germline. Although DNA demethylation of promoter-proximal CpGs of CT genes is linked to their expression in cancer, the mechanisms leading to demethylation are unknown. To elucidate such mechanisms we chose to study the Caco-2 colorectal cancer cell line during the course of its spontaneous differentiation in vitro, as we found CT genes, in particular PAGE2,-2B and SPANX-B, to be up-regulated during this process. Differentiation of these cells resulted in a mesenchymal-toepithelial transition (MET) as evidenced by the gain of epithelial markers CDX2, Claudin-4 and E-cadherin, and a concomitant loss of mesenchymal markers Vimentin, Fibronectin-1 and Transgelin. PAGE2 and SPAN-X up-regulation was accompanied by an increase in Ten-eleven translocation-2 (TET2) expression and cytosine 5-hydroxymethylation as well as the disassociation of heterochromatin protein 1 and the polycomb repressive complex 2 protein EZH2 from promoter-proximal regions of these genes. Reversal of differentiation resulted in down-regulation of PAGE2,-2B and SPANX-B, and induction of epithelial-to-mesenchymal transition (EMT) markers, demonstrating the dynamic nature of CT gene regulation in this model. © 2014 Yilmaz-Ozcan et al.
      Keywords
      In-vitro
      Dna Methylation
      Cancer/testis Antigens
      Myeloma Cells
      Es Cells
      Differentiation
      Caco-2
      5-hydroxymethylcytosine
      Demethylation
      5-methylcytosine
      Permalink
      http://hdl.handle.net/11693/12802
      Published Version (Please cite this version)
      http://dx.doi.org/10.1371/journal.pone.0107905
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