Telomerase and telomere stability: a new class of tumor suppressor?
Introduction of telomerase into normal cells provides telomere maintenance and an extended cellular life span, establishing the critical role of telomere attrition in cellular senescence. Additional data surrounding this observation suggest that expression of telomerase renders these "mortal" cells genomically stable with decreased frequencies of mutation, ultimately leading to continued proliferation without signs of changes typically associated with progression to a cancer-like phenotype. Interestingly, oncogenic insult after exogenous telomerase expression does not result in cellular transformation, yet addition of an oncogene first followed by telomerase does transform cells. Taken together, these results imply that order of addition is important for telomerase-mediated genomic protection and that telomerase expression is critical for the transformation process. The hypothesis proposed here is that telomerase, via its function in telomere stabilization, is capable of protecting cells from acquiring the required mutations and genomic instability necessary for malignant transformation, suggesting that telomerase is not an oncogene but may act as a novel class of tumor suppressor.
Elmore
L W
LW
Department of Pathology, Medical College of Virginia at Virginia Commonwealth University, Richmond 23298-0662, USA.
Holt
S E
SE
D000818:Animals; D002471:Cell Transformation, Neoplastic; D004795:Enzyme Stability; D016147:Genes, Tumor Suppressor; D006801:Humans; D019098:Telomerase; D016615:Telomere
D019098:Telomerase