Correlation of telomerase activity and telomere length to chemosensitivity.
Telomerase, which is selectively expressed in germline or cancer cells, is a ribonucleoprotein polymerase that contains an integral RNA with a short template element that can compensate telomeric loss by synthesizing TTAGGG repeats at chromosome ends. Telomeres appear to be critical for the integrity of chromosomes, stabilizing them from exonucleolytic degradation, preventing chromosome-to-chromosome fusions, and determining the maximum replicative capacity of cells. During the past decade, the roles of telomere length and telomerase activity have been investigated extensively in a variety of benign and malignant tumors of human origin, and stronger telomerase activity has been observed in more advanced tumors. Generally, the acquisition of telomerase activity in cancer cells is rather universal, which suggests that telomerase inhibition as a novel and potentially selective target for therapeutic intervention. Although a telomerase-specific inhibitor has not been found yet, the possible effect of anticancer agents on telomerase inhibition or the alteration of telomere length has been proposed. Recent development of TRAP assay not only increased the sensitivity but also allowed fast and efficient detection of telomerase activity. Technical aspects of this assay using self-established internal standard and nonradioisotopic detection method are addressed in this report. In addition, an overview of how to determine the telomere length is described.
Kiyozuka
Yasuhiko
Y
Department of Pathology II, Kansai Medical University, Osaka, Japan.
D000199:Actins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015139:Blotting, Southern; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012313:RNA / Q000737:chemistry; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure*; D013997:Time Factors; D014466:Ultraviolet Rays
D000199:Actins; D000970:Antineoplastic Agents; D009841:Oligonucleotides; D012313:RNA; D019098:Telomerase