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