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Aging, The Molecular Concepts

3.5. ARE CELLS EXPRESSING TELOMERASE "NORMAL"?

If telomerase is sufficient to provide cells with immortal proliferative capacity, it is commonly asked why is telomerase not a potent oncogene (e.g. are cells expressing telomerase more cancer prone)? Initial concerns that the introduction of telomerase into normal cells may actually increase the risk of abnormal cells have not proved true. One way to think about this is that special reproductive tissues maintain high levels of telomerase throughout life, and there is no increased incidence of cancers in these special cells when compared with other types of cancer (Table 3.III). The only known role of telomerase in cancer is to allow cells to overcome the generational clock imposed by cellular senescence. There is no evidence supporting any role for telomerase in the control of cell cycle, apoptosis, invasive growth properties, etc.

The cells with introduced telomerase extended the length of their telomeres and have continued to divide for 100 generations past the time they normally would stop dividing and continue to divide. The cells also are growing and dividing in a normal manner, giving rise to normal cells with the normal number of chromosomes. Experiments are still in progress to determine if we can advance these cells to a malignant phenotype by the introduction of viral oncoproteins, and tumor progressing agents (such as RAS etc).

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