title: Telomerase promotes efficient cell cycle kinetics and confers growth advantage to telomerase-negative transformed human cells.
abstract: 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.
authors: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
authors: H B
authors: HB
authors: Fleisig
authors: J M Y
authors: JM
authors: Wong
mesh_terms: D002448:Cell Adhesion; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D018920:Coculture Techniques; D016195:G2 Phase; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008938:Mitosis; D012313:RNA / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; C422952:telomerase RNA; D012313:RNA; C509186:TERT protein, human; D019098:Telomerase