Oncotarget

Research Papers:

A novel application of E1A in combination therapy with EGFR-TKI treatment in breast cancer

Chih-Ming Su, Ting-Yu Chang, Hui-Ping Hsu, Hui-Huang Lai, Jie-Ning Li, Yu-Jhen Lyu, Kuang-Tai Kuo, Ming-Te Huang, Jen-Liang Su and Pai-Sheng Chen _

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Oncotarget. 2016; 7:63924-63936. https://doi.org/10.18632/oncotarget.11737

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Abstract

Chih-Ming Su1,2, Ting-Yu Chang3, Hui-Ping Hsu4, Hui-Huang Lai5,6, Jie-Ning Li5,6, Yu-Jhen Lyu6, Kuang-Tai Kuo7,8, Ming-Te Huang2, Jen-Liang Su3,9,10,11, Pai-Sheng Chen5,6

1Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan, ROC

2Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC

3National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan, ROC

4Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan, ROC

5Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

6Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

7Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC

8Division of Thoracic Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan, ROC

9Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, ROC

10Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan, ROC

11Department of Biotechnology, Asia University, Taichung, Taiwan, ROC

Correspondence to:

Ming-Te Huang, email: [email protected]

Pai-Sheng Chen, email: [email protected]

Keywords: combination therapy, E1A

Received: May 04, 2016     Accepted: August 21, 2016     Published: August 31, 2016

ABSTRACT

Epidermal growth factor receptor (EGFR) is commonly overexpressed in breast cancer and is associated with poor clinical outcomes; however, an increasing number of patients have shown a poor effective response to EGFR tyrosine kinase inhibitors (EGFR-TKI). Here, we found that AXL expression was positively correlated with poor progression in breast cancer patients. Suppression of AXL by an anti-tumor protein, E1A, enhanced EGFR-TKI (gefitinib, erlotinib and lapatinib) sensitization, resulting in significant inhibition of tumor growth in breast cancer cells. Additionally, AXL overexpression dramatically impaired E1A-mediated EGFR-TKI sensitization. These findings show that downregulation of AXL expression by E1A contributes to sensitization to EGFR-TKI in breast cancer, suggesting that combinatorial therapy of AXL inhibitors or E1A gene therapy with EGFR-TKI may be a potential therapeutic strategy for treatment of breast cancer patients.


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