Telomerase promotes efficient cell cycle kinetics and confers growth advantage to telomerase-negative transformed human cells

摘要

Constitutive telomerase activity maintains telomere length and confers immortal phenotypes to human cancers. The prevalence of telomerase, rather than a homologous recombination-based mechanism, in telomere length maintenance suggests that telomerase also has auxiliary roles in tumorigenesis. Here, we investigate growth advantages provided by the telomerase enzyme in oncogene-transformed human cells that do not require telomerase activity for telomere length control. Our data suggest that in oncogene-transformed cells, telomerase activity accelerates cell growth kinetics in a cell cycle phase-specific manner and promotes anchorage-independent growth. Coculture experiments demonstrated that this growth advantage conferred by telomerase activity is not due to increased cellular cross-talk. Growth advantages provided by telomerase required all functional aspects of the enzyme. Dissociation-of-activity-in-telomerase mutants and other functionally defective versions of telomerase were unable to promote oncogene-transformed cell growth, suggesting that canonical telomerase activities may be involved. We conclude that telomerase provides advantages to oncogene-transformed human cells, thereby supporting the development of telomerase-based anticancer chemotherapies targeting these growth-promoting effects.