Epstein Barr Nuclear Antigen 1 Induced Lymphoma in Transgenic Mice

Coy, Joanna Lucy (1997) Epstein Barr Nuclear Antigen 1 Induced Lymphoma in Transgenic Mice. PhD thesis, University of Glasgow.

Abstract

Burkitt's lymphoma is a human B cell lymphoma which carries a charactenstic translocation resulting in c-myc deregulation due to juxtaposition of an immunoglobulin locus. There is a strong association between endemic Burkitt's lymphoma (eBL) and Epstein Barr virus (EBV). EBNA-1 is the only EBV latent antigen consistently expressed in eBL biopsies. Although tissue culture assays have not attributed any oncogenic activity to EBNA-1, two lines of Eli EBNA-1 transgenic mice succumb to monoclonal B cell lymphoma (Wilton and Levine, 1992, Wilson, Bell and Levine, 1996). The experiments described in this thesis were designed to explore wiat cellular factors contribute to Ev EBNA-1 induced lymphomas. The latency and penetrance of the phenotype are different between the two EBNA-1 transgenic lines; 100% of line 26 mice succumb to lymphoma in 4-12 months, 43% of line 59 mice succumb to lymphoma by 2 years of age. .An analysis of the RNA expression of the transgene has identified compex patterns of expression in both lines, with distinct differences between the lines. EBNA-1 is a functionally pleiotropic protein. The DNA binding activity of EBNA-1 is required for its essential role in viral DNA replication during latency, and also for its activity as a transcriptional transactivator. EBNA-1 DNA binding activity has been detected in line 26 tumour samples, but not in line 59 spleens, although the level of protein detected by Western analysis is higher in line 59 samples than in line 26 samples (Wilson and Levine, 1992). This may indicate that the level of EBNA-1 DNA binding activity is an important determinant of oncogenicity. Given that all the tumours in both lines are monoclonal, an attempt has been made to identify which oncogenes synergise with EBNA-1 in tumourigenesis. Several lines of evidence are strongly suggestive of a co-operation between EBNA-1 and deregulated c-myc in tumourigenesis, indicating that EBNA-1 may play a direct role in the pathogenesis of Burkitt's lymphoma.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: Joanna Wilson
• Keywords: Genetics, Oncology, Virology
• Date of Award: 1997
• Depositing User: Enlighten Team
• Unique ID: glathesis:1997-75273
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 21:22
• Last Modified: 19 Nov 2019 21:22
• URI: https://theses.gla.ac.uk/id/eprint/75273