Epigenetic regulation of telomerase in retinoid-induced differentiation of human leukemia cells

  • Authors:
    • William K. Love
    • Joel B. Berletch
    • Lucy G. Andrews
    • Trygve O. Tollefsbol
  • View Affiliations

  • Published online on: March 1, 2008     https://doi.org/10.3892/ijo.32.3.625
  • Pages: 625-631
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Abstract

Changes in the promoter methylation of hTERT, the gene that encodes telomerase, a ribonucleoprotein responsible for replacing telomeric repeats, have been demonstrated in differentiating cells where hTERT is inhibited, suggesting epigenetic regulation of hTERT. All-trans retinoic acid (ATRA) induces differentiation in human leukemia cells and has had significant clinical success treating promyelocytic leukemia in what is termed ‘differentiation therapy’. It is thought that the inhibition of telomerase is a target of retinoids and is closely tied to the differentiated phenotype. This study demonstrates the epigenetic changes associated with ATRA-induced inhibition of telomerase activity, including the hypoacetylation and hypermethylation of the hTERT promoter. Further, we have found changes in the differential expression of the three DNA methyltransferases during ATRA-induced differentiation of HL60 human leukemia cells. These results suggest that alteration of DNA methylation may play a role in the activation of telomerase in cancer cells and that epigenetic mechanisms may represent a target for differentiation therapy mechanisms. We propose that epigenetic changes in the hTERT promoter represent a stable locking mechanism in the retionoid-induced suppression of telomerase acitivity.

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March 2008
Volume 32 Issue 3

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

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Spandidos Publications style
Love WK, Berletch JB, Andrews LG and Tollefsbol TO: Epigenetic regulation of telomerase in retinoid-induced differentiation of human leukemia cells. Int J Oncol 32: 625-631, 2008
APA
Love, W.K., Berletch, J.B., Andrews, L.G., & Tollefsbol, T.O. (2008). Epigenetic regulation of telomerase in retinoid-induced differentiation of human leukemia cells. International Journal of Oncology, 32, 625-631. https://doi.org/10.3892/ijo.32.3.625
MLA
Love, W. K., Berletch, J. B., Andrews, L. G., Tollefsbol, T. O."Epigenetic regulation of telomerase in retinoid-induced differentiation of human leukemia cells". International Journal of Oncology 32.3 (2008): 625-631.
Chicago
Love, W. K., Berletch, J. B., Andrews, L. G., Tollefsbol, T. O."Epigenetic regulation of telomerase in retinoid-induced differentiation of human leukemia cells". International Journal of Oncology 32, no. 3 (2008): 625-631. https://doi.org/10.3892/ijo.32.3.625