EBV Regulates c-MYC, Apoptosis, and Tumorigenicity in Burkitt’s Lymphoma

Abstract

Epstein-Barr Virus (EBV) latency-associated gene expression in Burkitt’s lymphoma (BL) cells is limited to a small set of gene products, none of which are known to overtly influence cell growth potential. Designated type I latency, this program of viral gene expression is characteristic of BL tumor cells in vivo and is restricted to expression of the EBNA-1 protein, the BamHI-A rightward transcripts (BARTs), and two small non-coding RNAs, EBER-1 and EBER-2 (Arrand and Rymo 1982; Rowe et al. 1986; Gregory et al. 1990; Brooks et al. 1993; Fries et al. 1997). Notably, with the exception of EBNA-1, which is required for viral genome maintenance, none of these latency-associated gene products is essential for EBV-mediated immortalization of B lymphocytes in vitro (Swaminathan et al. 1991; Robertson et al. 1994). Consequently, a direct contribution of EBV to tumorigenic potential in BL has not been established. Thus, the dominant factor presumed to be responsible for maintenance of tumorigenicity in BL is the deregulated expression of the c-MYC proto-oncogene, which occurs as a consequence of chromosomal translocation (reviewed in Magrath 1990). This assumption, however, was challenged by the work of Takada and colleagues (Shimizu et al. 1994) who found that spontaneous loss of the EBV genome in the BL cell line Akata is associated with a concomitant loss of tumorigenic potential. The main objectives of this study were to define the contribution of EBV and individual latent gene products to tumorigenicity in BL using the Akata BL cell system