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.

journal_name

Oncogene

journal_title

Oncogene

authors

Fleisig HB,Wong JM

doi

10.1038/onc.2011.292

subject

Has Abstract

pub_date

2012-02-23 00:00:00

pages

954-65

issue

8

eissn

0950-9232

issn

1476-5594

pii

onc2011292

journal_volume

31

pub_type

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