Telomerase For The Development Of In Vitro Models Of Cancer Progression

The introduction of telomerase into some normal human cells resulted in bypass ofM1 and immortalization. After a doubling of their normal lifespan, these immortalized cells maintain a normal diploid karyotype and DNA damage and cell cycle checkpoints remained fully intact, suggesting that normal cells immortalized with telomerase do not develop additional cancer-associated changes. In cells expressing the Simian virus 40 Large T antigen for long periods of time followed by the introduction of an activated ras oncogene, the addition of telomerase appears to be sufficient for transformation into full tumorigenicity. Taken together, these results suggest that while telomerase expression per se does not result in genomic destabiliza-tion, in the context of underlying mutations, telomerase contributes to tumorigenicity by providing aberrant cells with an unlimited proliferative capacity.

The ability of telomerase to immortalize cells without altering the underlying genetic background has also been demonstrated in cells with inherited susceptibility syndromes, such as ataxia-telangiectasia, Bloom syndrome, xeroderma pigmentosum and premature ageing syndromes such as Werner syndrome and Hutchinson-Gilford pro-geria. Thus, telomerase may be an important tool for establishing premalignant cell lines which can be used for the development of in vitro models of cancer progression, for amassing large numbers of cells required for other assays or as standard cellular reagents for microarray analysis. Microarray is a novel technique which utilizes microchip technology to analyze cellular RNA for changes in patterns of genetic expression in mutated cells versus their normal counterparts.

The role of telomerase in cancer progression will undoubtedly represent a major continuing area of investigation in the field of cancer biology. The tight association between telomerase and cancer, the ability to generate immortalized human cell lines for studies of cancer progression and the development of telomerase inhibitors for use as anticancer agents all underscore the fundamental role of telomere maintenance as a major player in the development and continued unlimited growth of cancer cells.

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