Latent membrane protein 1 of Epstein-Barr virus plays an important role in the serum starvation resistance of Epstein-Barr virus-immortalized B lymphocytes

We have previously shown that SNU‐1103, which is a latency type III Epstein–Barr virus (EBV)‐transformed lymphoblastoid cell line (LCL) that was developed from a Korean cancer patient, resists serum starvation‐induced G1 arrest. In this study, we examined the role of latent membrane protein‐1 (LMP‐1) in serum starvation resistance, since LMP‐1 is known to be essential for EBV‐mediated immortalization of human B lymphocytes. The LMP‐1 gene from SNU‐1103 was introduced into the EBV‐negative BJAB cell line, and shown to be associated with resistance to G1 arrest during serum starvation. Western blot analyses of the LMP‐1‐transfected cells revealed several protein alterations as compared to vector‐transfected control cells. The expression of key cell‐cycle regulatory proteins was affected in the G1 phase: the expression of cyclin D3, CDK2, p27, and E2F‐4 was up‐regulated, and the expression of cyclin D2, CDK6, p21, and p103 was down‐regulated during serum starvation. These results imply that of the several EBV viral genes expressed in EBV‐negative B lymphoma cells, LMP‐1 mediates resistance to serum starvation‐induced G1 arrest. However, we cannot rule out the possibility that other EBV genes are also involved in the cell‐cycle progression of the EBV‐transformed LCL during serum starvation, since the altered protein expression profile of the LMP‐1 transfectants was distinct from that of the SNU‐1103 cells that expressed all of the EBV viral proteins. © 2004 Wiley‐Liss, Inc.