title: A novel application of E1A in combination therapy with EGFR-TKI treatment in breast cancer.
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.
authors: Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan, ROC.|Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC.
authors: Chih-Ming
authors: CM
authors: Su
authors: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan, ROC.
authors: Ting-Yu
authors: TY
authors: Chang
authors: Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan, ROC.
authors: Hui-Ping
authors: HP
authors: Hsu
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.|Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: Hui-Huang
authors: HH
authors: Lai
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.|Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: Jie-Ning
authors: JN
authors: Li
authors: Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: Yu-Jhen
authors: YJ
authors: Lyu
authors: Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC.|Division of Thoracic Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan, ROC.
authors: Kuang-Tai
authors: KT
authors: Kuo
authors: Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC.
authors: Ming-Te
authors: MT
authors: Huang
authors: National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli Country, Taiwan, ROC.|Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan, ROC.|Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan, ROC.|Department of Biotechnology, Asia University, Taichung, Taiwan, ROC.
authors: Jen-Liang
authors: JL
authors: Su
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.|Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: Pai-Sheng
authors: PS
authors: Chen
mesh_terms: D017500:Adenovirus E1A Proteins / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D018450:Disease Progression; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D000077156:Gefitinib; D015316:Genetic Therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000008:administration & dosage; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D017500:Adenovirus E1A Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D000077341:Lapatinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D000077156:Gefitinib; D000094963:Axl Receptor Tyrosine Kinase
keywords: E1A; combination therapy