The Epstein-Barr virus nuclear antigen-1 may act as a transforming suppressor of the HER2/neu oncogene.
It is known that the HER2/neu proto-oncogene is associated with a wide variety of human cancers and considered to be an attractive target for developing anti-cancer agents. We report here for the first time that the Epstein-Barr virus nuclear antigen-1 (EBNA1) suppresses the HER2/neu oncogene expression at the transcriptional level. Recombinant clones of EBNA1 were subcloned and stably transfected into HER2/neu-overexpressing human ovarian cancer SKOV3.ip1 cells. These EBNA1-containing clones down-regulated the endogenous production of p185(HER2/neu). In addition, the EBNA1-expressing stable transfectants showed reduced growth rate, low soft agarose colony-forming ability and tumorigenic potential as compared with the parental line. These data suggest that EBNA1 may act as a transforming suppressor of the HER2/neu oncogene.
Chuang
Tzu-Chao
TC
Graduate Institute of Life Sciences, National Defense Medical Center, National Defense University, Taipei, Taiwan.
Way
Tzong-Der
TD
Lin
Yen-Shing
YS
Lee
Ying-Chu
YC
Law
Sai-Lung
SL
Kao
Ming-Ching
MC
D016475:3T3 Cells; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D016147:Genes, Tumor Suppressor; D018734:Genes, erbB-2; D006801:Humans; D007700:Kinetics; D051379:Mice; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D019309:Epstein-Barr Virus Nuclear Antigens; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human; C417029:EBV-encoded nuclear antigen 1