Epigenetic Regulation of Telomerase in Retinoid-induced Differentiation of Human Leukemia Cells

Overview

Journal Int J Oncol

Specialty Oncology

Date 2008 Feb 23

PMID 18292940

Citations 13

Authors

William K Love

Joel B Berletch

Lucy G Andrews

Trygve O Tollefsbol

Affiliations

Soon will be listed here.

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 activity.

Citing Articles

Telomerase Regulation: A Role for Epigenetics.

Dogan F, Forsyth N Cancers (Basel). 2021; 13(6).

PMID: 33802026 PMC: 8000866. DOI: 10.3390/cancers13061213.

Involvement of epigenetic modification of TERT promoter in response to all-trans retinoic acid in ovarian cancer cell lines.

Losi L, Lauriola A, Tazzioli E, Gozzi G, Scurani L, DArca D J Ovarian Res. 2019; 12(1):62.

PMID: 31291979 PMC: 6617683. DOI: 10.1186/s13048-019-0536-y.

Modulation of Telomerase Activity in Cancer Cells by Dietary Compounds: A Review.

Eitsuka T, Nakagawa K, Kato S, Ito J, Otoki Y, Takasu S Int J Mol Sci. 2018; 19(2).

PMID: 29415465 PMC: 5855700. DOI: 10.3390/ijms19020478.

Regulatory role of G9a and LSD1 in the Transcription of Olfactory Receptors during Leukaemia Cell Differentiation.

Jung H, Chae Y, Kim J, Jeong O, Kook H, Seo S Sci Rep. 2017; 7:46182.

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Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition.

Ferguson L, Chen H, Collins A, Connell M, Damia G, Dasgupta S Semin Cancer Biol. 2015; 35 Suppl:S5-S24.

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