The Paradoxical Role of LMP1 in Carcinogenesis

MacDiarmid, J., Stevenson, D. and Wilson, J.B. (2002) The Paradoxical Role of LMP1 in Carcinogenesis. 10th International Symposium on Epstein-Barr Virus and Associated Malignant Diseases, Cairns, Australia, 16-21 Jul 2002.

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The role of LMP1 in predisposing epithelial cells to malignancy in vivo was investigated using the PyLMP1 transgenic mouse model, expressing LMP1 in the epidermis (Wilson et. al., 1990. Cell 61: 1315-1327). Skin chemical carcinogenesis studies revealed that LMP1 acts as a tumour promoter, augmenting the action of TPA (Curran et. al., 2001 Cancer Res 61:6730-6738). Treated PyLMP1 mice develop significantly more small papillomas than their wild type siblings. However, we have modelled the rate of lesion expansion and have found that the rate of growth of papillomas in PyLMP1 mice is significantly lower than that of controls. Also, LMP1 does not contribute to the conversion of papillomas to carcinomas. The INK4a locus encodes two tumour suppressor genes, p16INK4a and p19ARF (p14ARF in the mouse) and is regularly deleted in nasopharyngeal carcinomas (chromosome 9p21). The interplay between LMP1 and the INK4a locus was investigated using PyLMP1:INK4a null mice (Serrano et. al., 1996 Cell 85:27-37). With carcinogen treatment, it was found that loss of the INK4a locus overcomes the LMP1 mediated inhibition of papilloma size expansion. Furthermore, LMP1 and loss of the INK4a locus co-operate strongly during carcinogenesis, leading to large lesions which have a high rate of conversion to carcinoma.

Item Type:Conference or Workshop Item
Glasgow Author(s) Enlighten ID:Stevenson, Dr David and Wilson, Professor Joanna
Authors: MacDiarmid, J., Stevenson, D., and Wilson, J.B.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
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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