Blog
About

8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Telomerase and Telomeres in Endometrial Cancer

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Telomeres at the termini of human chromosomes are shortened with each round of cell division due to the “end replication problem” as well as oxidative stress. During carcinogenesis, cells acquire or retain mechanisms to maintain telomeres to avoid initiation of cellular senescence or apoptosis and halting cell division by critically short telomeres. The unique reverse transcriptase enzyme complex, telomerase, catalyzes the maintenance of telomeres but most human somatic cells do not have sufficient telomerase activity to prevent telomere shortening. Tissues with high and prolonged replicative potential demonstrate adequate cellular telomerase activity to prevent telomere erosion, and high telomerase activity appears to be a critical feature of most (80–90%) epithelial cancers, including endometrial cancer. Endometrial cancers regress in response to progesterone which is frequently used to treat advanced endometrial cancer. Endometrial telomerase is inhibited by progestogens and deciphering telomere and telomerase biology in endometrial cancer is therefore important, as targeting telomerase (a downstream target of progestogens) in endometrial cancer may provide novel and more effective therapeutic avenues. This review aims to examine the available evidence for the role and importance of telomere and telomerase biology in endometrial cancer.

          Related collections

          Most cited references 239

          • Record: found
          • Abstract: found
          • Article: not found

          The DNA damage response: ten years after.

          The DNA damage response (DDR), through the action of sensors, transducers, and effectors, orchestrates the appropriate repair of DNA damage and resolution of DNA replication problems, coordinating these processes with ongoing cellular physiology. In the past decade, we have witnessed an explosion in understanding of DNA damage sensing, signaling, and the complex interplay between protein phosphorylation and the ubiquitin pathway employed by the DDR network to execute the response to DNA damage. These findings have important implications for aging and cancer.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.

            We have found a novel activity in Tetrahymena cell free extracts that adds tandem TTGGGG repeats onto synthetic telomere primers. The single-stranded DNA oligonucleotides (TTGGGG)4 and TGTGTGGGTGTGTGGGTGTGTGGG, consisting of the Tetrahymena and yeast telomeric sequences respectively, each functioned as primers for elongation, while (CCCCAA)4 and two nontelomeric sequence DNA oligomers did not. Efficient synthesis of the TTGGGG repeats depended only on addition of micromolar concentrations of oligomer primer, dGTP, and dTTP to the extract. The activity was sensitive to heat and proteinase K treatment. The repeat addition was independent of both endogenous Tetrahymena DNA and the endogenous alpha-type DNA polymerase; and a greater elongation activity was present during macronuclear development, when a large number of telomeres are formed and replicated, than during vegetative cell growth. We propose that the novel telomere terminal transferase is involved in the addition of telomeric repeats necessary for the replication of chromosome ends in eukaryotes.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Telomeres and human disease: ageing, cancer and beyond.

               Maria Blasco (2005)
              Telomere length and telomerase activity are important factors in the pathobiology of human disease. Age-related diseases and premature ageing syndromes are characterized by short telomeres, which can compromise cell viability, whereas tumour cells can prevent telomere loss by aberrantly upregulating telomerase. Altered functioning of both telomerase and telomere-interacting proteins is present in some human premature ageing syndromes and in cancer, and recent findings indicate that alterations that affect telomeres at the level of chromatin structure might also have a role in human disease. These findings have inspired a number of potential therapeutic strategies that are based on telomerase and telomeres.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                17 May 2019
                2019
                : 9
                Affiliations
                1Liverpool Women's Hospital NHS Foundation Trust , Liverpool, United Kingdom
                2Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool , Liverpool, United Kingdom
                3The Ageing Biology Centre and Institute for Cell and Molecular Biosciences, Newcastle University , Newcastle upon Tyne, United Kingdom
                Author notes

                Edited by: Paola Gehrig, University of North Carolina at Chapel Hill, United States

                Reviewed by: Marilyn Huang, Sylvester Comprehensive Cancer Center, United States; Saori Furuta, University of Toledo, United States

                *Correspondence: Dharani K. Hapangama dharani@ 123456liv.ac.uk

                This article was submitted to Women's Cancer, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2019.00344
                6533802
                Copyright © 2019 Alnafakh, Adishesh, Button, Saretzki and Hapangama.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 6, Tables: 3, Equations: 0, References: 299, Pages: 29, Words: 23905
                Funding
                Funded by: Wellbeing of Women 10.13039/501100000325
                Funded by: Higher Committee for Education Development in Iraq 10.13039/501100009928
                Categories
                Oncology
                Review

                Oncology & Radiotherapy

                htert, hterc, telomerase, endometrium, terra, trap, endometrial cancer, telomere

                Comments

                Comment on this article