Epstein-Barr virus regulates c-MYC, apoptosis, and tumorigenicity in Burkitt lymphoma

Ingrid K. Ruf, Paul W. Rhyne, Hui Yang, Corina M. Borza, Lindsey M. Hutt-Fletcher, John L. Cleveland, Jeffery T. Sample

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

Loss of the Epstein-Barr virus (EBV) genome from Akata Burkitt lymphoma (BL) cells is coincident with a loss of malignant phenotype, despite the fact that Akata and other EBV-positive BL cells express a restricted set of EBV gene products (type I latency) that are not known to overtly affect cell growth. Here we demonstrate that reestablishment of type I latency in EBV- negative Akata cells restores tumorigenicity and that tumorigenic potential correlates with an increased resistance to apoptosis under growth-limiting conditions. The antiapoptotic effect of EBV was associated with a higher level of Bcl-2 expression and an EBV-dependent decrease in steady-state levels of c-MYC protein. Although the EBV EBNA-1 protein is expressed in all EBV-associated tumors and is reported to have oncogenic potential, enforced expression of EBNA-1 alone in EBV-negative Akata cells failed to restore tumorigenicity or EBV-dependent down-regulation of c-MYC. These data provide direct evidence that EBV contributes to the tumorigenic potential of Burkitt lymphoma and suggest a novel model whereby a restricted latency program of EBV promotes B-cell survival, and thus virus persistence within an immune host, by selectively targeting the expression of c-MYC.

Original languageEnglish (US)
Pages (from-to)1651-1660
Number of pages10
JournalMolecular and cellular biology
Volume19
Issue number3
DOIs
StatePublished - Mar 1999

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Ruf, I. K., Rhyne, P. W., Yang, H., Borza, C. M., Hutt-Fletcher, L. M., Cleveland, J. L., & Sample, J. T. (1999). Epstein-Barr virus regulates c-MYC, apoptosis, and tumorigenicity in Burkitt lymphoma. Molecular and cellular biology, 19(3), 1651-1660. https://doi.org/10.1128/MCB.19.3.1651