Telomerase is not an oncogene.
In the decade since the telomere hypothesis of cellular aging was proposed, the two essential genes for human telomerase were cloned and characterized, allowing experimental proof of the causal relationships between telomere loss and replicative senescence, and telomerase activation and immortalization. These relationships were established using a variety of cultured human cell types from both normal and tumor tissues, and were largely confirmed in the telomerase knockout mouse. Taken together, the data provide strong support for the potential utility of telomerase detection and inhibition for cancer, and telomerase activation for degenerative diseases. The specificity of the promoter for the telomerase catalytic gene and the antigenicity of the protein product, hTERT, provide additional strategies for killing telomerase-positive tumor cells. Unfortunately, the strong link between telomerase and cancer has led some to confuse telomerase activation with cancer, and others to overstate the cancer risk of telomerase activation therapies for degenerative diseases. This review clarifies the difference between telomerase, which does not cause growth deregulation, and oncogenes, which do. It also addresses the concept of telomerase repression as a tumor suppressor mechanism early in life, with detrimental tissue degeneration and tumor-promoting consequences late in life. This extended view of the telomere hypothesis helps explain how telomerase inhibition can be therapeutic in cancer patients, while controlled telomerase activation for degenerative diseases may actually reduce, rather than increase, the frequency of age-related tumorigenesis.
Harley
Calvin B
CB
Geron Corporation, Menlo Park, California, CA 94025, USA. charley@geron.com
D000375:Aging; D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D009857:Oncogenes; D019098:Telomerase / Q000235:genetics / Q000502:physiology*
D019098:Telomerase