Epstein-Barr virus LMP2A accelerates MYC-induced lymphomagenesis

R. Bultema; R. Longnecker; M. Swanson-Mungerson

doi:10.1038/onc.2008.492

Epstein-Barr virus LMP2A accelerates MYC-induced lymphomagenesis

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

^*Corresponding author for this work

Microbiology-Immunology

Research output: Contribution to journal › Article › peer-review

43 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-X_L 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 language	English (US)
Pages (from-to)	1471-1476
Number of pages	6
Journal	Oncogene
Volume	28
Issue number	11
DOIs	https://doi.org/10.1038/onc.2008.492
State	Published - Mar 19 2009

Keywords

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

ASJC Scopus subject areas

Genetics
Molecular Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/onc.2008.492

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title = "Epstein-Barr virus LMP2A accelerates MYC-induced lymphomagenesis",

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.",

keywords = "Bcl, Burkitt's lymphoma, Epstein-Barr virus, LMP2A, Myc, Transgenic models",

author = "R. Bultema and R. Longnecker and M. Swanson-Mungerson",

note = "Funding Information: 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 l-MYC transgenic mice.",

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AU - Bultema, R.

AU - Longnecker, R.

AU - Swanson-Mungerson, M.

N1 - Funding Information: 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 l-MYC transgenic mice.

PY - 2009/3/19

Y1 - 2009/3/19

N2 - 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.

AB - 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.

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Epstein-Barr virus LMP2A accelerates MYC-induced lymphomagenesis

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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