Poznan University of Medical Sciences, Department of Clinical Chemistry and Molecular Diagnostics, Poland.
Biochem Cell Biol. 2011 Aug;89(4):359-76. doi: 10.1139/o11-037. Epub 2011 Jul 26.
Since telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells, it has become a very promising target for anti-cancer therapy. A correlation between short telomere length and increased mortality was revealed in many studies. The telomerase expression/activity appears to be one of the most crucial factors to study to improve cancer therapy and prevention. However, this multisubunit enzymatic complex can be regulated at various levels. Thus, several strategies have been proposed to control telomerase in cancer cells such as anti-sense technology against TR and TERT, ribozymes against TERT, anti-estrogens, progesterone, vitamin D, retinoic acid, quadruplex stabilizers, telomere and telomerase targeting agents, modulation of interaction with other proteins involved in the regulation of telomerase and telomeres, etc. However, the transcription control of key telomerase subunits seems to play the crucial role in whole complexes activity and cancer cells immortality. Thus, the research of telomerase regulation can bring significant insight into the knowledge concerning stem cells metabolism but also ageing. This review summarizes the current state of knowledge of numerous telomerase regulation mechanisms at the transcription level in human that might become attractive anti-cancer therapy targets.
由于端粒酶已被认为是区分癌细胞和正常细胞的相关因素，因此它已成为癌症治疗的一个非常有前途的靶点。许多研究揭示了端粒较短与死亡率增加之间的相关性。端粒酶的表达/活性似乎是研究提高癌症治疗和预防的最重要因素之一。然而，这种多亚基酶复合物可以在多个水平上进行调节。因此，已经提出了几种控制癌细胞中端粒酶的策略，例如针对 TR 和 TERT 的反义技术、针对 TERT 的核酶、抗雌激素、孕激素、维生素 D、视黄酸、四链体稳定剂、端粒和端粒酶靶向剂、调节与参与端粒酶和端粒调节的其他蛋白质的相互作用等。然而，关键端粒酶亚基的转录控制似乎在整个复合物的活性和癌细胞的永生化中起着至关重要的作用。因此，对端粒酶调控的研究可以深入了解与干细胞代谢和衰老有关的知识。这篇综述总结了目前在人类转录水平上对多种端粒酶调控机制的认识，这些机制可能成为有吸引力的抗癌治疗靶点。
