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Epstein–Barr virus LMP2A accelerates MYC-induced lymphomagenesis

Oncogene volume 28, pages 1471–1476 (2009)Cite this article

Abstract

Despite the identification of Epstein–Barr virus (EBV) in tumors of Burkitt's lymphoma (BL) over 40 years ago, the exact contribution of EBV to BL is undefined. EBV encodes for multiple proteins in latent B cells that affect B cell survival and activation. One such protein, latent membrane protein 2A (LMP2A), protects B cells from numerous pro-apoptotic stimuli. Therefore, we tested whether LMP2A protects B cells from apoptosis induced by aberrant c-MYC expression that precedes and dominates BL. We crossed LMP2A-transgenic mice (LMP2A-Tg), in which all B cells express LMP2A, to a transgenic mouse that expresses a BL translocation of myc (λ-MYC-Tg mice). LMP2A promotes proliferation and protects B cells from MYC-induced apoptosis in λ-MYC-Tg mice. LMP2A also accelerates the development of lymphoma in LMP2A/λ-MYC-Tg mice. Finally, LMP2A increases the expression of Bcl-XL in both pre-tumor B cells and tumor cells, suggesting a mechanism for LMP2A-mediated B cell survival in the presence of MYC. These results support a hypothesis that EBV LMP2A promotes tumor development by protecting pre-tumor B cells that would normally apoptose after the c-myc translocation.

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Acknowledgements

RL is a John Edward Porter Professor in Biomedical Research and supported by the Public Health Service Grants CA62234 and CA73507 from the NCI. The authors thank Dr Herbert C Morse III, the NIAID, and the NCI for the λ-MYC transgenic mice.

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  1. Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    R Bultema, R Longnecker & M Swanson-Mungerson

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  1. R Bultema
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  2. R Longnecker
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Correspondence to R Longnecker.

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Bultema, R., Longnecker, R. & Swanson-Mungerson, M. Epstein–Barr virus LMP2A accelerates MYC-induced lymphomagenesis. Oncogene 28, 1471–1476 (2009). https://doi.org/10.1038/onc.2008.492

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