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 expr...

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Bibliographic Details
Published in:FEBS letters 2002-12, Vol.532 (1), p.135-142
Main Authors: Chuang, Tzu-Chao, Way, Tzong-Der, Lin, Yen-Shing, Lee, Ying-Chu, Law, Sai-Lung, Kao, Ming-Ching
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Carcinoma - genetics
Carcinoma - metabolism
Carcinoma - pathology
Cell Division
Cell Transformation, Neoplastic
EBNA1
Epstein-Barr Virus Nuclear Antigens - genetics
Epstein-Barr Virus Nuclear Antigens - pharmacology
Female
Genes, erbB-2
Genes, Tumor Suppressor
HER2/neu
Humans
Kinetics
Mice
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Promoter Regions, Genetic
Receptor, ErbB-2 - biosynthesis
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - physiology
Transcription, Genetic
Transfection
Tumor Cells, Cultured
Tumorigenicity
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(02)03658-X