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

Author(s): Love WK (Love, William K.), Berletch JB (Berletch, Joel B.), Andrews LG (Andrews, Lucy G.), Tollefsbol TO (Tollefsbol, Trygve O.)
Source: INTERNATIONAL JOURNAL OF ONCOLOGY
Volume: 32 Issue: 3 Pages: 625-631 Published: MAR 2008

Telomerase activity is repressed in differentiated cells thus allowing senescence and apoptosis to occur in due time because of telomere shortening with repeated cell division. Cancer cells exhibit a high level of telomerase activity leading to their 'immortal' state.

All-trans retinoic acid (ATRA) is capable of inducing differentiation of human leukemia cells and has been proven to be significantly successful in treating promyelocytic leukemia. This treatment modality is termed as 'differentiation therapy'.

Previous studies have shown that ATRA down-regulates telomerase but its exact mechanism of action has not been clearly elucidated. This study explores the ATRA-induced epigenetic changes of telomerase activity. These changes include hypermethylation and hypoacetylation of the hTERT (human telomerase gene) promoter in HL60 human leukemia cells. Differential expression of the three DNA methyltransferases has also been observed.

These results suggest that altered DNA methylation may lead to activation of telomerase in cancer cells and epigenetic changes can be exploited for 'differentiation therapy' mechanisms in other tumors.

Good luck everyone... 8)
Sohinee Sarkar.
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