The Paradoxical Role of EBV LMP1 in Carcinogenesis

Stevenson, D., Charalambous, C. and Wilson, J.B. (2004) The Paradoxical Role of EBV LMP1 in Carcinogenesis. Keystone Symposia: Mouse Models of Human Cancer, Keystone, CO, USA, 17-22 Feb 2004.

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In contrast to its role as an oncoprotein, the latent membrane protein-1 (LMP1) of Epstein-Barr virus has also been found to have growth inhibitory effects. As such, its role in EBV associated malignancies, such as nasopharyngeal carcinoma (NPC) remains unclear. Skin chemical carcinogenesis studies with LMP1 expressing transgenic mice have revealed that LMP1 acts as a tumour promoter, augmenting the action of TPA. However, we have modelled the rate of lesion expansion and have found that the rate of growth of papillomas in PyLMP1 mice is significantly slower than that of controls. The INK4a locus (encoding p16INK4a and p19ARF [p14ARF in the mouse]) is regularly deleted in NPC. In PyLMP1:INK4a null mice following carcinogen treatment, it was found that loss of the INK4a locus overcomes the LMP1 mediated papilloma growth inhibition. LMP1 and loss of the INK4a locus cooperate leading to increased numbers of lesions which have a high rate of conversion to carcinoma. The phenotype of LMP1 mice strongly resembles transgenic TGFalpha mice and indeed TGFalpha is upregulated very early in LMP1 induced lesion development. Later, as keratoacanthotic lesions become necrotic, p16INK4a and MMP9 are upregulated. We hypothesize that LMP1 acts, at least in part, through TGFalpha. Further, that the observed lesion growth inhibition involves p16INK4a. This would explain the frequent loss of the INK4a locus in NPC.

Item Type:Conference or Workshop Item
Glasgow Author(s) Enlighten ID:Stevenson, Dr David and Wilson, Professor Joanna
Authors: Stevenson, D., Charalambous, C., 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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