Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer


Shaw, RJ ORCID: 0000-0002-5157-4042, Omar, MM, Rokadiya, S, Kogera, FA, Lowe, D, Hall, GL, Woolgar, JA, Homer, J, Liloglou, T ORCID: 0000-0003-0460-1404, Field, JK ORCID: 0000-0003-3951-6365 et al (show 1 more authors) (2009) Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer. BRITISH JOURNAL OF CANCER, 101 (1). pp. 139-144.

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Abstract

<h4>Background</h4>Cytoglobin (Cygb) was first described in 2002 as an intracellular globin of unknown function. We have previously shown the downregulation of cytoglobin as a key event in a familial cancer syndrome of the upper aerodigestive tract.<h4>Methods</h4>Cytoglobin expression and promoter methylation were investigated in sporadic head and neck squamous cell carcinoma (HNSCC) using a cross-section of clinical samples. Additionally, the putative mechanisms of Cygb expression in cancer were explored by subjecting HNSCC cell lines to hypoxic culture conditions and 5-aza-2-deoxycitidine treatment.<h4>Results</h4>In clinically derived HNSCC samples, CYGB mRNA expression showed a striking correlation with tumour hypoxia (measured by HIF1A mRNA expression P=0.013) and consistent associations with histopathological measures of tumour aggression. CYGB expression also showed a marked negative correlation with promoter methylation (P=0.018). In the HNSCC cell lines cultured under hypoxic conditions, a trend of increasing expression of both CYGB and HIF1A with progressive hypoxia was observed. Treatment with 5-aza-2-deoxycitidine dramatically increased CYGB expression in those cell lines with greater baseline promoter methylation.<h4>Conclusion</h4>We conclude that the CYGB gene is regulated by both promoter methylation and tumour hypoxia in HNSCC and that increased expression of this gene correlates with clincopathological measures of a tumour's biological aggression.

Item Type: Article
Additional Information: Shaw, R J,Omar, M M,Rokadiya, S, Kogera, F A, Lowe, D, Hall, G L, Woolgar, J A; Homer, J, Liloglou, T, Field, J K, Risk, J M Research Support, Non-U.S. Gov't England British journal of cancer Br J Cancer. 2009 Jul 7;101(1):139-44. ## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords: CYGB, head and neck squamous cell carcinoma, hypoxia, HIF1-a, methylation
Subjects: ?? RK ??
Divisions: Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Dentistry
Depositing User: Symplectic Admin
Date Deposited: 02 Oct 2009 09:38
Last Modified: 16 Dec 2022 12:30
DOI: 10.1038/sj.bjc.6605121
Publisher's Statement : © 2009 Cancer Research UK . This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. First published in British Journal of Cancer (2009) 101, 139–144. doi:10.1038/sj.bjc.6605121 'Cytoglobin is upregulated by tumour hypoxia and silenced by promoter hypermethylation in head and neck cancer' R J Shaw, M M Omar, S Rokadiya, F A Kogera, D Lowe, G L Hall, J A Woolgar, J Homer, T Liloglou, J K Field, and J M Risk. http://dx.doi.org/10.1038/sj.bjc.6605121 .
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URI: https://livrepository.liverpool.ac.uk/id/eprint/1178
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