Phenotypic alterations induced by the Hong Kong‐prevalent Epstein‐Barr virus‐encoded LMP1 variant (2117‐LMP1) in nasopharyngeal epithelial cells

Epstein‐Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), a common cancer in Hong Kong. The EBV‐encoded LMP1 protein is believed to play an important role in cell transformation. We have previously identified a prevalent LMP1 variant (2117‐LMP1) that is expressed in 86% of primary NPC in Hong Kong. In this study, the biologic phenotypes induced by 2117‐LMP1 were compared with those of the prototypic B95.8‐LMP1 in an immortalized nasopharyngeal epithelial cell line, NP69. The 2117‐LMP1 could induce cell proliferation and resistance to apoptosis induced by growth factor deprivation. Expression of 2117‐LMP1 also suppressed expression of p16, p21 and Bax but induced expression of CDK2 and A20. Compared with B95.8‐LMP1, 2117‐LMP1 could induce a higher migration ability in NP69 cells but was less efficient in inducing morphologic changes, anchorage‐independent growth and cell invasion. Relatively weaker ability of 2117‐LMP1 than B95.8‐LMP1 in upregulation of vimentin, VEGF and MMP9 as well as in downregulation of E‐cadherin was observed. 2117‐LMP1 could activate higher level of NF‐κB activity in HEK 293 cells than B95.8‐LMP1. The present study supports a role of 2117‐LMP1 in NPC development by enhancing cell proliferation, cell death inhibition and migration in premalignant nasopharyngeal epithelial cells. Furthermore, our study reveals significant functional differences between 2117‐LMP1 and the prototypic B95.8‐LMP1. Our results provide insights into the pathologic significance of this prevalent LMP1 variant, 2117‐LMP1, in the development of NPC in the Hong Kong population. © 2004 Wiley‐Liss, Inc.