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

Int J Cancer. 2004 May 10;109(6):919-25. doi: 10.1002/ijc.20051.


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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC2-CDC28 Kinases / metabolism
  • Cadherins / metabolism
  • Cell Division
  • Cell Movement
  • Cell Survival
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • DNA-Binding Proteins
  • Herpesvirus 4, Human / physiology*
  • Hong Kong
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Matrix Metalloproteinase 9 / metabolism
  • NF-kappa B / metabolism
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / virology*
  • Nuclear Proteins
  • Phenotype
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism
  • Viral Matrix Proteins / physiology*
  • bcl-2-Associated X Protein


  • BAX protein, human
  • CDKN1A protein, human
  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Vascular Endothelial Growth Factor A
  • Viral Matrix Proteins
  • bcl-2-Associated X Protein
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Matrix Metalloproteinase 9