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Telomerase and the endocrine system

Abstract

Telomeres are nucleoprotein complexes located at the ends of chromosomes that have a critical role in the maintenance of chromosomal integrity. This involvement is based on complex secondary and tertiary structures that rely on DNA–DNA, DNA–protein and protein–protein interactions. De novo synthesis and maintenance of telomere repeats is controlled by telomerase, a specialized complex that consists of a telomerase RNA component and a protein component—telomerase reverse transcriptase. When telomerase is silent (its default state in differentiated somatic cells), chromosomes shorten with every cell division, thus limiting the lifespan of the cells (the process of senescence) and preventing unlimited cell proliferation, which might eventually lead to the development of cancer. During this process, occasionally, a cell can activate telomerase, which stabilizes short telomeres and enables immortalization—a process essential for malignant transformation. Thus, although telomere erosion is a barrier to malignant progression, paradoxically, in certain circumstances it might also trigger tumorigenesis. A number of studies have demonstrated unequivocally that reactivation of telomerase in the presence of short telomeres is one of the most common features of human cancers, including those of the endocrine system.

Key Points

  • Telomerase is a reverse transcriptase enzyme that maintains chromosome ends

  • During tumorigenesis, telomerase contributes to the stabilization of short telomeres thus immortalizing cells and contributing to their continued proliferation

  • Telomerase is expressed in most endocrine cancers and its activity is positively correlated with the malignant phenotype

  • Measurement of telomerase activity has been proposed for the differential diagnosis of benign and malignant endocrine lesions

  • This enzyme has also been proposed as a potential target in cancer therapy; several strategies have been developed to target telomerase, including antisense therapies and vaccines

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Figure 1: The location and structure of the TERT gene.
Figure 2: A schematic representation of the process that leads to cell immortalization.
Figure 3: The proposed methods to inhibit telomerase.

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M. Capezzone, S. Cantara and S. Marchisotta researched data for the article. All authors contributed to discussion of the content. F. Pacini wrote, reviewed and edited the manuscript before submission.

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Correspondence to Furio Pacini.

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Pacini, F., Cantara, S., Capezzone, M. et al. Telomerase and the endocrine system. Nat Rev Endocrinol 7, 420–430 (2011). https://doi.org/10.1038/nrendo.2011.52

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