Radiation-induced modulation of immunogenic genes in tumor cells is regulated by both histone deacetylases and DNA methyltransferases

  • Authors:
    • Ercan Cacan
    • Susanna F. Greer
    • Charlie Garnett-Benson
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  • Published online on: October 7, 2015     https://doi.org/10.3892/ijo.2015.3192
  • Pages: 2264-2275
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Abstract

Radiation treatment is a pivotal therapy for several cancer types, including colorectal cancer. It has been shown that sublethal doses of radiation modulate gene expression, making tumor cells more susceptible to T-cell-mediated immune attack. We have recently shown that low dose radiation enhances expression of multiple death receptors (Fas, DR4 and DR5) and co-stimulatory molecules (4-1BBL and OX-40L) in colorectal cancer (CRC) cells; however, it is unclear how ionizing radiation (IR) enhances expression of these molecules mechanistically. In the present study, we elucidate the molecular mechanisms by which radiation controls expression of these molecules in CRC. Here we report that, enhanced expression of these genes following radiation treatment of CRC cells is due, in part, to changes in DNA methylation and histone acetylation. We observed that radiation (5 Gy) significantly increased histone acetylation at the promoter regions of 4-1BBL, Fas and DR5 but not OX-40L. However, radiation did not induce changes in the global levels of acetylated histone H3 suggesting specificity of IR-induced changes. Furthermore, evaluation of epigenetic controlling enzymes revealed that IR did not alter overall cellular levels of HDACs (HDAC1, HDAC2 or HDAC3) or DNMTs (DNMT1, DNMT3a, or DNMT3b). Instead, radiation decreased binding of HDAC2 and HDAC3 at the promoter regions of Fas and 4-1BBL, respectively. Radiation also resulted in reduced DNMT1 at both the Fas and 4-1BBL promoter regions but not a control gene. We conclude that single dose radiation can influence the expression of immune response relevant genes in colorectal tumor cells by altering the binding of epigenetic enzymes, and modulating histone acetylation, at specific gene promoters.
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December-2015
Volume 47 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Cacan E, Greer SF and Garnett-Benson C: Radiation-induced modulation of immunogenic genes in tumor cells is regulated by both histone deacetylases and DNA methyltransferases. Int J Oncol 47: 2264-2275, 2015
APA
Cacan, E., Greer, S.F., & Garnett-Benson, C. (2015). Radiation-induced modulation of immunogenic genes in tumor cells is regulated by both histone deacetylases and DNA methyltransferases. International Journal of Oncology, 47, 2264-2275. https://doi.org/10.3892/ijo.2015.3192
MLA
Cacan, E., Greer, S. F., Garnett-Benson, C."Radiation-induced modulation of immunogenic genes in tumor cells is regulated by both histone deacetylases and DNA methyltransferases". International Journal of Oncology 47.6 (2015): 2264-2275.
Chicago
Cacan, E., Greer, S. F., Garnett-Benson, C."Radiation-induced modulation of immunogenic genes in tumor cells is regulated by both histone deacetylases and DNA methyltransferases". International Journal of Oncology 47, no. 6 (2015): 2264-2275. https://doi.org/10.3892/ijo.2015.3192