Dysregulation of HER2/HER3 signaling axis in Epstein-Barr virus-infected breast carcinoma cells

Jiun Han Lin, Ching Hwa Tsai, Jan Show Chu, Jeou Yuan Chen, Kenzo Takada, Jin Yuh Shew

Research output: Contribution to journalArticle

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Abstract

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 lympho-blastoid 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 BARFO was detected. We next showed that BARFO 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.

Original languageEnglish
Pages (from-to)5705-5713
Number of pages9
JournalJournal of Virology
Volume81
Issue number11
DOIs
Publication statusPublished - Jun 2007

Fingerprint

Human herpesvirus 4
Human Herpesvirus 4
breast neoplasms
Breast Neoplasms
cells
Epstein-Barr Virus Infections
MCF-7 Cells
Agar
Phosphatidylinositol 3-Kinase
Virus Latency
agar
Mitogen-Activated Protein Kinase Kinases
Small Interfering RNA
phosphatidylinositol 3-kinase
direct contact
small interfering RNA
Breast
Up-Regulation
infection
Epithelial Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Dysregulation of HER2/HER3 signaling axis in Epstein-Barr virus-infected breast carcinoma cells. / Lin, Jiun Han; Tsai, Ching Hwa; Chu, Jan Show; Chen, Jeou Yuan; Takada, Kenzo; Shew, Jin Yuh.

In: Journal of Virology, Vol. 81, No. 11, 06.2007, p. 5705-5713.

Research output: Contribution to journalArticle

Lin, Jiun Han ; Tsai, Ching Hwa ; Chu, Jan Show ; Chen, Jeou Yuan ; Takada, Kenzo ; Shew, Jin Yuh. / Dysregulation of HER2/HER3 signaling axis in Epstein-Barr virus-infected breast carcinoma cells. In: Journal of Virology. 2007 ; Vol. 81, No. 11. pp. 5705-5713.
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