Ageing and cancer: the telomere and telomerase connection.
Telomeres are repetitive DNA sequences at the ends of linear chromosomes. Telomerase, a cellular reverse transcriptase, helps stabilize telomere length in human stem, reproductive and cancer cells by adding TTAGGG repeats onto the telomeres. Each time a telomerase-negative cell divides some telomeric sequences are lost. When telomeres are short, cells enter an irreversible growth arrest state called replicative senescence. In most instances cells become senescent before they can become cancerous, thus the growth arrest induced by short telomeres may be a potent anti-cancer mechanism. Since most cancers express telomerase, maintenance of telomere stability is likely to be required for the long-term viability of tumours. Inhibition of telomerase results in gradual erosion of telomeres followed by cessation of proliferation or apoptosis, and thus may be a promising target for cancer therapy. Introduction of the telomerase catalytic protein component into telomerase-silent cells is sufficient to restore telomerase activity and extend cellular life span. However, cells with introduced telomerase are not cancer cells since they have not accumulated the other changes needed to become cancerous. This indicates that telomerase-induced telomere length manipulations may have utility for tissue engineering and for dissecting the molecular mechanisms underlying genetic diseases including cancer.
Shay
J W
JW
University of Texas Southwestern Medical Center at Dallas, Department of Cell Biology, 5323 Harry Hines Boulevard, Dallas, TX 75390-9039, USA.
Wright
W E
WE
D000375:Aging / Q000235:genetics; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics; D019098:Telomerase / Q000502:physiology*; D016615:Telomere / Q000502:physiology*
D019098:Telomerase