Synergism of BARF1 with Ras induces malignant transformation in primary primate epithelial cells and human nasopharyngeal epithelial cells.

Although it is well known that nasopharyngeal carcinoma (NPC) is closely related with Epstein-Barr virus (EBV), few data are available about which and how EBV-expressed gene is involved in the carcinogenesis of human nasopharyngeal epithelial cells. EBV-encoded BARF1 (BamH I-A right frame 1) gene has been shown to be oncogenic and capable of inducing malignant transformation in BALB/c3T3 and NIH3T3 cells as well as in human B-cell lines Louckes and Akata. It remains unclear, however, whether BARF1 can transform primate or human epithelial cells. Here, we have shown that overexpression of H-Ras gene transformed BARF1-immortalized PATAS cells into malignant cell line. Furthermore, we found that cooperation of BARF1 with H-Ras and SV40 T antigens was sufficient to transform nonmalignant human nasopharyngeal epithelial NP69 cells when serially introduced BARF1 and H-Ras into the SV40 T antigens-immortalized NP69 cells. Taken together, these results demonstrated that the cooperation of BARF1 with Ras suffices to transform primary primate epithelial cell PATAS. Similarly, BARF1 together with H-Ras and SV40 T can transform human epithelial cell NP69, thereby indicating that BARF1 could be involved in the NPC pathogenesis in combination with additional genetic changes.