Inhibition of telomerase limits the growth of human cancer cells

Telomerase is a ribonucleoprotein enzyme that maintains the protective stru ctures at the ends of eukaryotic chromosomes, called telomeres. In most hum an somatic cells, telomerase expression is repressed, and telomeres shorten progressively with each cell division. In contrast, most human tumors expr ess telomerase, resulting in stabilized telomere length. These observations indicate that telomere maintenance is essential to the proliferation of tu mor cells. We show here that expression of a mutant catalytic subunit of hu man telomerase results in complete inhibition of telomerase activity, reduc tion in telomere length and death of tumor cells. Moreover, expression of t his mutant telomerase eliminated tumorigenicity in vivo. These observations demonstrate that disruption of telomere maintenance limits cellular lifesp an in human cancer cells, thus validating human telomerase reverse transcri ptase as an important target for the development of anti-neoplastic therapi es.