Cooperative interactions among p53, bcl-2 and Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma cells

Pathol Int. 2004 Jul;54(7):475-85. doi: 10.1111/j.1440-1827.2004.01654.x.

Abstract

Interactions among p53, bcl-2 and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) in nasopharyngeal carcinoma (NPC) cells were evaluated by gene cotransfections. The data showed that bcl-2 expression was not only able to prevent the growth suppression induced by wild-type p53 but was also paradoxically able to inhibit the growth enhancement induced by mutant p53. Latent membrane protein 1 was shown to be capable of overcoming the growth inhibition induced by wild-type p53 and the synergistic cooperation with bcl-2 to enhance cellular growth. Latent membrane protein 1 could also cooperate with mutant p53 to provide a growth advantage for NPC cells. Most NPC revealed detectable overexpression of p53, and the majority of those were a wild type possibly responding to EBV infection. The coexpression of bcl-2 and LMP1 was thought to inhibit the growth suppression induced by wild-type p53 in NPC. But there was no associated expression between LMP1 and bcl-2 because we demonstrated that transfected LMP1 failed to induce bcl-2 expression in NPC cells in contrast to the findings in B cells. It is theorized that the cooperative expression of bcl-2 and LMP1 exists in the majority of NPC, while a minority of NPC have cooperative expression of LMP1 and mutant p53. Each cooperative interaction could play an important role in the development and progression of NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nasopharyngeal Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Transfection
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*

Substances

  • EBV-associated membrane antigen, Epstein-Barr virus
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Viral Matrix Proteins