title: Epstein-Barr virus small RNAs potentiate tumorigenicity of Burkitt lymphoma cells independently of an effect on apoptosis.
abstract: The tumorigenic potential of the Burkitt lymphoma (BL) cell line Akata is dependent on the restricted latency program of Epstein-Barr virus (EBV) that is characteristically maintained in BL tumors. Within these cells, EBV-mediated inhibition of apoptosis correlates with an up-regulation of BCL-2 levels in concert with a down-regulation in c-MYC expression that occurs under growth-limiting conditions. Here we addressed whether EBV's effects on apoptosis and tumorigenicity are mediated by the EBV small RNAs EBER-1 and EBER-2. Stable expression of the EBERs in EBV-negative Akata BL cells, at levels comparable to those in EBV-positive cells, significantly enhanced the tumorigenic potential of EBV-negative BL cells in SCID mice, but did not fully restore tumorigenicity relative to EBV-positive Akata cells. Furthermore, wild-type or greater levels of EBER expression in EBV-negative Akata cells did not promote BL cell survival. These data therefore suggest that EBV can contribute to BL through at least two avenues: an EBER-dependent mechanism that enhances tumorigenic potential independent of a direct effect on apoptosis, and a second mechanism, mediated by an as-yet-unidentified EBV gene(s), that offsets the proapoptotic consequences of deregulated c-MYC in BL.
authors.affiliation: Program in Viral Oncogenesis and Tumor Immunology, Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: I K
authors.initials: IK
authors.lastname: Ruf
authors.forename: P W
authors.initials: PW
authors.lastname: Rhyne
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.forename: J L
authors.initials: JL
authors.lastname: Cleveland
authors.forename: J T
authors.initials: JT
authors.lastname: Sample
mesh_terms: D000818:Animals; D017209:Apoptosis; D002051:Burkitt Lymphoma / Q000473:pathology / Q000821:virology*; D002461:Cell Line, Transformed; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D012367:RNA, Viral