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

Eur J Cancer. 2011 Aug;47(12):1908-18. doi: 10.1016/j.ejca.2011.04.012. Epub 2011 May 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Angiogenesis Inhibitors / pharmacology
  • Blotting, Western
  • Bronchi / chemistry
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • CpG Islands / genetics
  • DNA Methylation
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Histones / metabolism
  • Humans
  • Immunophilins / metabolism
  • Interleukins / genetics*
  • Interleukins / metabolism*
  • Interleukins / pharmacology
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / prevention & control
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / metabolism
  • Respiratory Mucosa / chemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / analysis
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Histones
  • Interleukins
  • RNA, Messenger
  • Receptors, Interleukin
  • Vascular Endothelial Growth Factor A
  • interleukin-20 receptor
  • interleukin-22 receptor
  • Vascular Endothelial Growth Factor Receptor-2
  • Immunophilins
  • interleukin 20