Telomeres, telomerase, and telomerase inhibition: clinical implications for cancer.
Telomeres are located at the ends of eukaryotic chromosomes. The enzyme telomerase synthesized them, and they are responsible for maintaining the lengths of chromosomes. Absence of telomerase is associated with telomere shortening and aging of somatic cells, but high telomerase activity is observed in over 90% of human cancer cells. Although the disappearance of telomerase with aging is considered a natural defense against development of cancer, it is not known what triggers the reappearance of telomerase in cancer cells. Telomerase activity is directly correlated with the expression of its active catalytic component, the human telomerase reverse transcriptase (hTERT), which is controlled primarily at the level of transcription. An earlier paper discussed the relationship of telomerase with aging. In this article, the contemporary literature is reviewed to explore the associations between telomerase, telomerase inhibition, and cancer. Because most cancers occur in old age, with the aging of the population, the number of people suffering from cancer is expected to increase in the coming decades. It is not known what roles telomerase and hTERT play in the complex relationship between aging and cancer. Data from experimental studies suggest that telomerase assay could potentially play a role in the diagnosis and prognosis of cancers. There is also evidence that telomerase inhibitors might be used as anticancer agents. As the knowledge of the relationships between telomerase and cancer and between telomerase and aging advances, it is hoped that more about the interacting relationships between telomerase, aging, and cancer will be learned.
Ahmed
Ali
A
Division of Gerontology and Geriatric Medicine, Department of Medicine, School of Medicine, University of Alabama at Birmingham and Heart Failure Clinic and Section of Gerontology, VA Medical Center, Birmingham, Alabama 35294-2041, USA. aahmed@uab.edu
Tollefsbol
Trygve
T
D000368:Aged; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D004268:DNA-Binding Proteins; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology*; D011379:Prognosis; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000201:enzymology / Q000502:physiology
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019098:Telomerase