Skip to main content
Top
Published in: Digestive Diseases and Sciences 4/2010

01-04-2010 | Original Article

Upregulation and CpG Island Hypomethylation of the TRF2 Gene in Human Gastric Cancer

Authors: Wenjie Dong, Lifu Wang, Xiaobing Chen, Pinghu Sun, Yunlin Wu

Published in: Digestive Diseases and Sciences | Issue 4/2010

Login to get access

Abstract

The telomere-binding protein TRF2 regulates both telomere protection and telomere length. The fact that TRF2 is up-regulated in some tumors indicates that TRF2 plays a role in cancer. However, the role of TRF2 in gastric cancer has not been fully understood. The aim of this study is to evaluate the expression pattern of TRF2 in gastric cancer and examine the potential mechanism of TRF2 regulation. Our study revealed that the expression of TRF2 analyzed by immunohistochemistry was significantly higher in gastric cancers compared to noncancerous tissues. Moreover, TRF2 methylation was detected in six of 30 (20%) primary gastric cancers and 18 of 30 (60%) paired normal tissues, and the downregulation of TRF2 was strongly correlated with the methylation status (P < 0.001). Our results suggest that hypomethylation might contribute to the upregulation of TRF2 in gastric cancers and this overexpression may play a role in the pathogenesis of gastric cancers.
Literature
7.
go back to reference Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet. 2000;25:347–352. doi:10.1038/77139.CrossRefPubMed Zhu XD, Kuster B, Mann M, Petrini JH, de Lange T. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet. 2000;25:347–352. doi:10.​1038/​77139.CrossRefPubMed
8.
go back to reference Bradshaw PS, Stavropoulos DJ, Meyn MS. Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage. Nat Genet. 2005;37:193–197. doi:10.1038/ng1506.CrossRefPubMed Bradshaw PS, Stavropoulos DJ, Meyn MS. Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage. Nat Genet. 2005;37:193–197. doi:10.​1038/​ng1506.CrossRefPubMed
9.
go back to reference Oh BK, Kim YJ, Park C, Park YN. Up-regulation of telomere-binding proteins, TRF1, TRF2, and TIN2 is related to telomere shortening during human multistep hepatocarcinogenesis. Am J Pathol. 2005;166:73–80.PubMed Oh BK, Kim YJ, Park C, Park YN. Up-regulation of telomere-binding proteins, TRF1, TRF2, and TIN2 is related to telomere shortening during human multistep hepatocarcinogenesis. Am J Pathol. 2005;166:73–80.PubMed
10.
go back to reference Munoz P, Blanco R, Flores JM, Blasco MA. XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer. Nat Genet. 2005;37:1063–1071. doi:10.1038/ng1633.CrossRefPubMed Munoz P, Blanco R, Flores JM, Blasco MA. XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer. Nat Genet. 2005;37:1063–1071. doi:10.​1038/​ng1633.CrossRefPubMed
11.
go back to reference Richter T, Saretzki G, Nelson G, Melcher M, Olijslagers S, von Zglinicki T. TRF2 overexpression diminishes repair of telomeric single-strand breaks and accelerates telomere shortening in human fibroblasts. Mech Ageing Dev. 2007;128:340–345. doi:10.1016/j.mad.2007.02.003.CrossRefPubMed Richter T, Saretzki G, Nelson G, Melcher M, Olijslagers S, von Zglinicki T. TRF2 overexpression diminishes repair of telomeric single-strand breaks and accelerates telomere shortening in human fibroblasts. Mech Ageing Dev. 2007;128:340–345. doi:10.​1016/​j.​mad.​2007.​02.​003.CrossRefPubMed
12.
go back to reference Zhang YW, Zhang ZX, Miao ZH, Ding J. The telomeric protein TRF2 is critical for the protection of A549 cells from both telomere erosion and DNA double-strand breaks driven by salvicine. Mol Pharmacol. 2008;73:824–832. doi:10.1124/mol.107.039081.CrossRefPubMed Zhang YW, Zhang ZX, Miao ZH, Ding J. The telomeric protein TRF2 is critical for the protection of A549 cells from both telomere erosion and DNA double-strand breaks driven by salvicine. Mol Pharmacol. 2008;73:824–832. doi:10.​1124/​mol.​107.​039081.CrossRefPubMed
13.
go back to reference Bellon M, Datta A, Brown M, et al. Increased expression of telomere length regulating factors TRF1, TRF2 and TIN2 in patients with adult T-cell leukemia. Int J Cancer. 2006;119:2090–2097. doi:10.1002/ijc.22026.CrossRefPubMed Bellon M, Datta A, Brown M, et al. Increased expression of telomere length regulating factors TRF1, TRF2 and TIN2 in patients with adult T-cell leukemia. Int J Cancer. 2006;119:2090–2097. doi:10.​1002/​ijc.​22026.CrossRefPubMed
Metadata
Title
Upregulation and CpG Island Hypomethylation of the TRF2 Gene in Human Gastric Cancer
Authors
Wenjie Dong
Lifu Wang
Xiaobing Chen
Pinghu Sun
Yunlin Wu
Publication date
01-04-2010
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 4/2010
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-009-0810-8

Other articles of this Issue 4/2010

Digestive Diseases and Sciences 4/2010 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.