Kyo Satoru, Inoue Masaki
Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Japan.
Oncogene. 2002 Jan 21;21(4):688-97. doi: 10.1038/sj.onc.1205163.
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.
在几乎90%的人类癌症中可观察到端粒酶激活，而在体细胞来源的正常组织中则未观察到，因此端粒酶激活是多步骤致癌过程中的关键一步。对端粒酶调控的更深入理解不仅可为癌症进展提供分子基础，还可作为一种操纵端粒酶活性的潜在治疗方式。端粒酶调控研究的最新进展表明，端粒酶激活在多个步骤实现，包括端粒酶逆转录酶（hTERT）基因的转录和转录后水平。尽管已提出许多潜在的重要端粒酶激活机制，但目前没有一个模型能完全解释端粒酶的肿瘤特异性激活，这表明需要进一步广泛分析。本综述总结了端粒酶调控的近期研究工作，并讨论了如何克服这一情况。
