The N-terminal domain of EBNA1 acts as a suppressor of the HER2/neu oncogene

Cancer Lett. 2009 Jan 18;273(2):273-80. doi: 10.1016/j.canlet.2008.08.013. Epub 2008 Sep 20.


HER2/neu oncogene-mediated malignancy is clearly associated with various human cancers. Therefore, HER2/neu targeting is an effective approach to cancer therapy. We have previously demonstrated that Epstein-Barr virus nuclear antigen-1 (EBNA1) can suppress HER2/neu oncogene expression, although EBNA1 itself has oncogenic potential. Here, we found that the N-terminal domain of EBNA1 alone, named EBNA1-NT, which contains the N-terminal region of amino acid residues 1-86 of EBNA1, is required and sufficient to suppress HER2/neu oncogene expression at the transcriptional level. Furthermore, in EBNA1-NT-transfected HER2/neu-overexpressing cells, we found EBNA1-NT could down-regulate the endogenous production of p185(HER2/neu), lower transformation ability, sensitize paclitaxel-induced apoptosis and decrease tumorigenic potential. These data suggest that EBNA1-NT may act as a repressor of the HER2/neu oncogene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Transformation, Neoplastic
  • Epstein-Barr Virus Nuclear Antigens / metabolism*
  • Female
  • Genetic Therapy / methods
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Oncogenes
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology
  • Protein Structure, Tertiary
  • Receptor, ErbB-2 / metabolism*


  • Epstein-Barr Virus Nuclear Antigens
  • Receptor, ErbB-2