Role of Inflammation and Oxidative Stress in Epstein-Barr Virus Oncogene Induced Carcinogenesis

Qureshi, A., Hannigan, A. and Wilson, J.B. (2010) Role of Inflammation and Oxidative Stress in Epstein-Barr Virus Oncogene Induced Carcinogenesis. Keystone Symposium on Role Inflammation in Cancer, Keystone, CO, USA, 2010.

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Abstract

We have been studying the role of inflammation and oxidative stress in a transgenic mouse model of carcinogenesis. In our model, we have used the primary oncogene of Epstein-Barr virus (EBV) encoding the latent membrane protein-1 (LMP1) (Stevenson et al 2005, Cancer Research 65, 8826-8835). EBV is tightly associated with nasopharyngeal carcinoma (NPC), a tumour which is so highly infiltrated with lymphocytes that it is frequently referred to as a lymphoepithelioma. In our transgenic mice (L2LMP1 mice), the transgene is expressed in the epidermis. The skin of these mice (most notably in hairless regions such as ears) develops a progressive pathology from birth, initiating with hyperplasia and hypervascularization, dramatically worsening with time, increasing inflammation, necrosis, ulceration, leading to keratocanthoma and papilloma formation, which can progress on to carcinoma development. We have shown that the preneoplastic (inflamed) skin of the transgenic mice is heavily infiltrated with T-cells, mast cells and neutrophils. Affected tissues also show upregulation of several chemokines and cytokines including CD30, CD30L, CD40, L-Selectin, IL-3, IL-1β and macrophage inflammatory proteins. We have also shown increased deposition of immunoglobulins and increased levels of complement component 3 (C-3) in the inflamed preneoplastic skin. By proteomic analysis, we have demonstrated massive upregulation of an enzymatically inactive chitinase-like protein, called chitinase-3-like-4 (chi3l4 or YM2) in the transgenic epidermis (Hannigan et al 2007, Journal of Proteome Research, 6,3422-3432). Such massive upregulation of this protein may suggest a role in inflammation induced carcinogenesis. We have found a decrease in SOD1 levels and increase in H2O2 in the affected skin suggesting that the tissue is also under oxidative stress. Furthermore our preliminary data reveals evidence of DNA damage in the affected tissues which could result from excess of reactive oxygen species. These data will be presented and discussed. Dissecting the role of inflammation and oxidative stress in this model of carcinogenesis may provide new insights for therapeutic designs.

Item Type:Conference or Workshop Item
Status:Published
Refereed:No
Glasgow Author(s) Enlighten ID:Wilson, Professor Joanna
Authors: Qureshi, A., Hannigan, A., and Wilson, J.B.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences

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