Human telomerase expression regulation

Abstract

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.