IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF

Baird, Anne-Marie, Gray , Steven G., & O'Byrne, Kenneth J. (2011) IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF. European Journal of Cancer, 47(12), pp. 1908-1918.

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Abstract

Background

IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung cancer (NSCLC) by down regulating COX-2.

Methods

The expression of IL-20 and its cognate receptors (IL-20RA/B and IL-22R1) was examined in a series of resected fresh frozen NSCLC tumours. Additionally, the expression and epigenetic regulation of this family was examined in normal bronchial epithelial and NSCLC cell lines. Furthermore, the effect of IL-20 on VEGF family members was examined.

Results

The expression of IL-20 and its receptors are frequently dysregulated in NSCLC. IL-20RB mRNA was significantly elevated in NSCLC tumours (p < 0.01). Protein levels of the receptors, IL-20RB and IL-22R1, were significantly increased (p < 0.01) in the tumours of NSCLC patients. IL-20 and its receptors were found to be epigenetically regulated through histone post-translational modifications and DNA CpG residue methylation. In addition, treatment with recombinant IL-20 resulted in decreased expression of the VEGF family members at the mRNA level.

Conclusions

This family of genes are dysregulated in NSCLC and are subject to epigenetic regulation. Whilst the anti-angiogenic properties of IL-20 require further clarification, targeting this family via epigenetic means may be a viable therapeutic option in lung cancer treatment. © 2011 Elsevier Ltd. All rights reserved.

Impact and interest:

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ID Code: 64809
Item Type: Journal Article
Refereed: Yes
Keywords: DNA CpG methylation, Epigenetics, Histone post-translational modification, IL-20, IL-20RA, IL-20RB, IL-22R1, Non-small cell lung cancer, cytokine receptor, histone, interleukin 20, interleukin 20 receptor A, interleukin 20 receptor B, interleukin 22 receptor 1, messenger RNA, recombinant cytokine, unclassified drug, vasculotropin, article, bronchus mucosa, cancer cell culture, controlled study, CpG island, DNA methylation, down regulation, frozen section, gene control, lung non small cell cancer, priority journal, protein expression, protein processing, Acetylation, Angiogenesis Inhibitors, Blotting, Western, Bronchi, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Cell Proliferation, Chromatin Immunoprecipitation, CpG Islands, Down-Regulation, Enzyme-Linked Immunosorbent Assay, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Histones, Humans, Immunophilins, Interleukins, Lung Neoplasms, Neovascularization, Pathologic, Receptors, Interleukin, Respiratory Mucosa, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2
DOI: 10.1016/j.ejca.2011.04.012
ISSN: 0959-8049
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2011 Pergamon
Deposited On: 26 Nov 2013 03:17
Last Modified: 30 Jul 2014 02:58

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