Epstein-Barr virus LMP2A accelerates MYC-induced lymphomagenesis

R. Bultema, R. Longnecker*, M. Swanson-Mungerson

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Scopus citations

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 (γ-MYC-Tg mice). LMP2A promotes proliferation and protects B cells from MYC-induced apoptosis in γ-MYC-Tg mice. LMP2A also accelerates the development of lymphoma in LMP2A/γ-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.

Original languageEnglish (US)
Pages (from-to)1471-1476
Number of pages6
JournalOncogene
Volume28
Issue number11
DOIs
StatePublished - Mar 19 2009

Keywords

  • Bcl
  • Burkitt's lymphoma
  • Epstein-Barr virus
  • LMP2A
  • Myc
  • Transgenic models

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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