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

// Chih-Ming Su 1, 2 , Ting-Yu Chang 3 , Hui-Ping Hsu 4 , Hui-Huang Lai 5, 6 , Jie-Ning Li 5, 6 , Yu-Jhen Lyu 6 , Kuang-Tai Kuo 7, 8 , Ming-Te Huang 2 , Jen-Liang Su 3, 9, 10, 11 , Pai-Sheng Chen 5, 6 1 Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan, ROC 2 Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC 3 National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan, ROC 4 Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan, ROC 5 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC 6 Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC 7 Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC 8 Division of Thoracic Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan, ROC 9 Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, ROC 10 Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan, ROC 11 Department of Biotechnology, Asia University, Taichung, Taiwan, ROC Correspondence to: Ming-Te Huang, email: mthuant@tmu.edu.tw Pai-Sheng Chen, email: bio.benson@gmail.com 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.