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

Ruf IK, Rhyne PW, Yang H, Borza CM, Hutt-Fletcher LM, Cleveland JL, Sample JT
Mol Cell Biol. 1999 19 (3): 1651-60

PMID: 10022853 · PMCID: PMC83959 · DOI:10.1128/mcb.19.3.1651

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.

MeSH Terms (12)

Apoptosis Burkitt Lymphoma Cell Division Cell Transformation, Viral Down-Regulation Epstein-Barr Virus Nuclear Antigens Herpesvirus 4, Human HL-60 Cells Humans Proto-Oncogene Proteins c-myc Tumor Cells, Cultured Virus Latency

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