title: β-Catenin overexpression is associated with gefitinib resistance in non-small cell lung cancer cells.
abstract: BACKGROUND
  Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) presents great challenges in the treatment of non-small cell lung cancer (NSCLC) patients, while the mechanisms are still not well understood. The β-catenin signaling pathway has been found to be associated with chemoresistance and can activate the EGFR and its downstream pathways. This study aimed to investigate the role of β-catenin in acquired resistance to EGFR-TKIs in NSCLC cell lines.
  
  
  METHODS
  The expression and transcriptional activity of β-catenin were measured in both the NSCLC cell line PC9 and its sub-line PC9/AB(2) which has acquired resistance to gefitinib. Knockdown and overexpression of β-catenin in the PC9/AB(2) and PC9 cells were performed. The cell survival rate and the activation of the EGFR and its downstream pathways were detected in the two cell lines after transfection.
  
  
  RESULTS
  Nuclear translocation of β-catenin was increased in the PC9/AB(2) cells and the baseline expression of members of the β-catenin signaling pathway was also higher in the PC9/AB(2) cells. Knocking down the expression of β-catenin increased the sensitivity of the PC9/AB(2) cells to gefitinib by blocking the activation of the EGFR downstream pathways, while β-catenin overexpression improved PC9 cells resistance to gefitinib by enhancing the activation of the EGFR and its downstream signaling.
  
  
  CONCLUSIONS
  β-catenin plays an important role in acquired resistance to EGFR-TKIs in NSCLC cell lines and may be a potential therapeutic target for NSCLC patients who have failed to respond to targeted therapy.
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: dilay_123@yahoo.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: gupanjiayou@sina.com.
authors.forename: Pan
authors.initials: P
authors.lastname: Gu
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: cczhou2000@126.com.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Haematology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: lab410817@126.com.
authors.forename: Aibin
authors.initials: A
authors.lastname: Liang
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: Hillary_ren@126.com.
authors.forename: Shenxiang
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: GYLIUFANG@HOTMAIL.COM.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: yuzeng77@hotmail.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: yunjinwuhope@126.com.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: zhaoyingmin80@126.com.
authors.forename: Yinmin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Haematology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: binbin2004_20@hotmail.com.
authors.forename: Binbin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: zongzong1986@126.com.
authors.forename: Zongmei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address: yixhxf@yahoo.com.cn.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Yi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D051176:beta Catenin; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: Epidermal growth factor receptor; Gefitinib; Non-small cell lung cancer; Resistance; Tyrosine kinase inhibitors; β-catenin