Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 42, Pages 17945-17950Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0907994106
Keywords
viral oncogenesis; Burkitt's lymphoma; apoptosis
Categories
Funding
- Public Health Service [CA133063, CA73507]
- National Cancer Institute
- Carcinogenesis Training Program [T32CA009560]
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Although Epstein-Barr virus (EBV) is linked to Burkitt's lymphoma (BL), the role of the virus in lymphomagenesis is unclear. LMP2A, encoded by EBV, can be detected in BL biopsies and has prosurvival functions. We generated mice expressing MYC and LMP2A in B cells. LMP2A/lambda-MYC mice show greatly accelerated tumor onset. Similar to previous work, we found p53 mutations in lambda-MYC tumors; however, we detected no mutations in the rapidly arising LMP2A/lambda-MYC tumors. We further demonstrate that the p53 pathway is functionally intact in LMP2A/lambda-MYC tumors, which have increased levels of PUMA and sensitivity to p53 activation by Nutlin. This work shows that LMP2A can permit tumorigenesis in the presence of an intact p53 pathway, identifying an important contribution of EBV to BL.
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