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 telom ere attrition in cellular senescence. Additional data surrounding this obse rvation suggest that expression of telomerase renders these "mortal" cells genomically stable with decreased frequencies of mutation, ultimately leadi ng to continued proliferation without signs of changes typically associated with progression to a cancer-like phenotype. Interestingly, oncogenic insu lt after exogenous telomerase expression does not result in cellular transf ormation, yet addition of an oncogene first followed by telomerase does tra nsform cells. Taken together, these results imply that order of addition is important for telomerase-mediated genomic protection and that telomerase e xpression is critical for the transformation process. The hypothesis propos ed here is that telomerase, via its function in telomere stabilization. is capable of protecting cells from acquiring the required mutations and genom ic instability necessary for malignant transformation, suggesting that telo merase is not an oncogene but may act as a novel class of tumor suppressor. Mol. Carcinog. 28. 1-4, 2000. (C) 2000 Wiley-Liss. Inc.