Telomerase activation, cellular immortalization and cancer

The maintenance of specialized nucleoprotein structures termed telomeres is essential for chromosome stability. Without new synthesis of telomeres at chromosome ends the chromosomes shorten with progressive cell division, eve ntually triggering either replicative senescence or apoptosis when telomere length becomes critically short, The regulation of telomerase activity in human cells plays a significant role in the development of cancer, Telomera se is tightly repressed in the vast majority of normal human somatic cells but becomes activated during cellular immortalization and in cancers, While the mechanisms for telomerase activation in cancers have not been fully de fined, they include telomerase catalytic subunit gene (hTERT) amplification and trans-activation of the hTERT promoter by the myc oncogene product. Ec topic expression of hTERT is sufficient to restore telomerase activity in c ells that lack the enzyme and can immortalize many cell types. Understandin g telomerase biology will eventually lead to several clinically relevant te lomerase-based therapies. These applications include inhibiting or targetin g telomerase as a novel antineoplastic strategy and using cells immortalize d by telomerase for therapeutic applications.