Complex regulatory mechanisms of telomerase activity in normal and cancer cells: how can we apply them for cancer therapy?
Telomerase activation is observed in almost 90% of human cancers but not in normal tissues of somatic origin and thus is a critical step for multistep carcinogenesis. A more thorough understanding of telomerase regulation may provide not only a molecular basis of cancer progression but also as a way to manipulate telomerase activity as a potential therapeutic modality. Recent progress in studies on telomerase regulation has shown that telomerase activation is achieved at various steps, including transcriptional and post-transcriptional levels of the telomerase reverse transcriptase (hTERT) gene. Although a number of potentially important mechanisms of telomerase activation have been proposed, none of the current models can fully explain tumor-specific activation of telomerase, suggesting a need for further extensive analysis. This review includes a summary of recent works on telomerase regulation and a discussion of how we can overcome this situation.
Kyo
Satoru
S
Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Japan. satoruky@med.kanazawa-u.ac.jp
Inoue
Masaki
M
D017398:Alternative Splicing; D000970:Antineoplastic Agents / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D010766:Phosphorylation; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D000970:Antineoplastic Agents; D001685:Biological Factors; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D019098:Telomerase