The N-terminal domain of EBNA1 acts as a suppressor of the HER2/neu oncogene.
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.
Liu
Jah-Yao
JY
Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan.
Chuang
Tzu-Chao
TC
Way
Tzong-Der
TD
Tsai
Tzung-Chieh
TC
Hu
Chih-Lin
CL
Liu
Guang-Yaw
GY
Wang
Shan-Shue
SS
Chung
Jing-Gung
JG
Kao
Ming-Ching
MC
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D019309:Epstein-Barr Virus Nuclear Antigens; D018719:Erb-b2 Receptor Tyrosine Kinases