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bcl-xL and RAG genes are induced and the response to IL-2 enhanced in EμEBNA-1 transgenic mouse lymphocytes

Oncogene volume 21, pages 5182–5187 (2002)Cite this article

Abstract

We have described transgenic mice expressing Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) in B-cells which show a predisposition to lymphoma. To investigate the underlying oncogenic mechanisms, we have cross bred transgenic strains of mice, examined the pre-tumour B-cell phenotype and investigated the expression levels of selected cellular genes as a response to EBNA-1 expression. We have found that bcl-xL and the recombination activating genes (RAG) 1 and 2 are induced in pre-neoplastic samples of EBNA-1 expressing mice. Induction of bcl-xL may explain the observed redundancy in lymphomagenesis between transgenic EBNA-1 and bcl-2. In addition, bone marrow cells derived from the EμEBNA-1 mice show a greater capacity for cultured growth compared to controls, particularly in the presence of IL-2. Notably, bcl-xL expression is responsive to IL-2. These data shed new light on the potential contribution of EBNA-1 to EBV associated tumorigenicity as well as to the viral life cycle and open a potential avenue for therapeutic intervention.

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Acknowledgements

This work was supported by grants from the Leukaemia Research Fund and the Lady Tata Memorial Trust. The Bcl-2-Ig transgenic mouse line was a kind gift from S Korsmeyer. Numerous individuals sent plasmid constructs for our use in generating probe fragments for which we are grateful. We thank Bill Cushley for assistance with the FACS analyses and David Stevenson for critical reading of the manuscript.

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  1. Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G11 6NU, UK

    Penelope Tsimbouri, Mark E Drotar, Joanna L Coy & Joanna B Wilson

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  1. Penelope Tsimbouri
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  2. Mark E Drotar
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  3. Joanna L Coy
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Correspondence to Joanna B Wilson.

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Tsimbouri, P., Drotar, M., Coy, J. et al. bcl-xL and RAG genes are induced and the response to IL-2 enhanced in EμEBNA-1 transgenic mouse lymphocytes. Oncogene 21, 5182–5187 (2002). https://doi.org/10.1038/sj.onc.1205490

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