This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lin, J.-H.
Right arrow Articles by Shew, J.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lin, J.-H.
Right arrow Articles by Shew, J.-Y.

 Previous Article  |  Next Article 

Journal of Virology, June 2007, p. 5705-5713, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.00076-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Dysregulation of HER2/HER3 Signaling Axis in Epstein-Barr Virus-Infected Breast Carcinoma Cells{triangledown}

Jiun-Han Lin,1 Ching-Hwa Tsai,2 Jan-Show Chu,3,4 Jeou-Yuan Chen,5 Kenzo Takada,6 and Jin-Yuh Shew1*

Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan,1 Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan,2 Department of Pathology, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan,3 Department of Pathology, Taipei Medical University Hospital, Taipei 11031, Taiwan,4 Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan,5 Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan6

Received 11 January 2007/ Accepted 9 March 2007

The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer has been of long-standing interest to the field. Breast epithelial cells can be infected by EBV through direct contact with EBV-bearing lymphoblastoid cells, and EBV infection has recently been shown to confer breast cancer cells an increased resistance to chemotherapeutic drugs. In this study, we established EBV-infected breast cancer MCF7 and BT474 cells and demonstrated that EBV infection promotes tumorigenic activity of breast cancer cells. Firstly, we showed that the EBV-infected MCF7-A and BT474-A cells exhibited increased anchorage-independent growth in soft agar. The increased colony formation capacity in soft agar was associated with increased expression and activation of HER2/HER3 signaling cascades, as evidenced by the findings that the treatment of HER2 antibody trastuzumab (Herceptin), phosphatidylinositol 3-kinase inhibitor, or MEK inhibitor completely abolished the tumorigenic capacity. In the EBV-infected breast cancer cells, the expression of EBV latency genes including EBNA1, EBER1, and BARF0 was detected. We next showed that BARF0 alone was sufficient to efficiently up-regulate HER2/HER3 expression and promoted tumorigenic activity in MCF7 and BT474 cells by the use of both overexpression and small interfering RNA knock-down. Collectively, we demonstrated that EBV-encoded BARF0 promotes the tumorigenic activity of breast cancer cells through activation of HER2/HER3 signaling cascades.

* Corresponding author. Mailing address: Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Room 818, No. 1, Sec. 1, Jen-Ai Road, Taipei 10051, Taiwan. Phone: 886-2-2312-3456, ext. 8216. Fax: 886-2-2391-5295. E-mail: jyshew{at}ntu.edu.tw

{triangledown} Published ahead of print on 21 March 2007.

Journal of Virology, June 2007, p. 5705-5713, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.00076-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Najy, A. J., Day, K. C., Day, M. L. (2008). The Ectodomain Shedding of E-cadherin by ADAM15 Supports ErbB Receptor Activation. J. Biol. Chem. 283: 18393-18401 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»