Establishment and characterization of gastric carcinoma cell clones expressing LMP2A of Epstein-Barr virus.

Although Epstein-Barr virus (EBV) has been detected in 5-15% of gastric carcinoma (GC) cases, the mechanism by which EBV contributes to its tumorigenesis remains unclear. Only a subset of EBV latent proteins such as EBV nuclear antigen-1 and latent membrane protein 2A (LMP2A) are expressed in EBV-associated GC (EBVaGC) cases. In this study, to elucidate the role of LMP2A in the tumorigenesis of EBVaGC, we established permanent cell lines expressing LMP2A. The LMP2A gene was cloned from a naturally EBV-infected EBVaGC cell line, SNU-719 and transduced into an EBV-negative GC cell line, AGS, using a retroviral vector. The sequence of SNU-719 LMP2A showed several conserved variations compared to that of the prototype EBV strain B95-8 LMP2A. Four of seven established cell clones expressed LMP2A protein at detectable levels. These cell clones did not show enhanced cell growth compared to control cells in normal or low serum-containing medium. Furthermore, LMP2A expression had no effect on colony forming ability of the cell clones in soft agar. Our results suggest that LMP2A alone has little effect on tumorigenesis of EBVaGC.