title: Rad51 in regulating the radiosensitivity of non-small cell lung cancer with different epidermal growth factor receptor mutation status.
abstract: Non-small cell lung cancer (NSCLC) harboring kinase-domain mutations in epidermal growth factor receptors (EGFR) has been observed to be sensitive to ionizing radiation (IR). We explore Rad51-dependent homologous recombination (HR) DNA repair in regulating radiosensitivity in two NSCLC cell lines with different EGFR mutation status.
  
  
  
  NSCLC cell lines, wild-type EGFR A549 and mutant EGFR H820 with an in-frame deletion in exon 19 of EGFR (ΔE746-E750), were cultured. Radiosensitivity was estimated by colony forming assay. Rad51 expression was evaluated by quantitative real time-polymerase chain reaction and Western-blot. Lentiviral small hairpin ribonucleic acid-Rad51 and ΔE746-E750 deletion mutant EGFR were constructed and transfected into cells. Flowcytometry assay was used to analyze DNA double strand breaks, cell cycle alterations, and apoptosis.
  
  
  
  A549 had a higher survival factor (SF)2 (0.66 vs. 0.44) and lower α/β value (4.07 vs. 9.01). Compared with the A549 cell, the H820 cell exhibited defective arrest in the S-phase, a higher rate of G2/M accumulation, early apoptosis, and residual γ-H2AX. Downregulated Rad51 expression decreased SF2 (0.42 vs. 0.31) and increased the α/β ratio (7.51 vs. 10.5), G2/M accumulation, early apoptosis, and γ-H2AX in two cell lines. H820 had a low IR-induced Rad51 expression and nuclear translocation. Exogenous expression of the ΔE746-E750 deletion mutant EGFR caused the A549 cell to become more radiosensitive.
  
  
  
  An EGFR mutated NSCLC cell line is sensitive to IR , which is correlated with reduced IR-induced Rad51 expression and nuclear translocation. The signaling pathway of EGFR maintaining Rad51 protein levels maybe a novel lung cancer therapeutic target to overcome radioresistance.
authors.affiliation: Thoracic Oncology West China Hospital Sichuan University Chengdu China; State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Thoracic Oncology West China Hospital Sichuan University Chengdu China; State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China.
authors.forename: Guomin
authors.initials: G
authors.lastname: Luo
authors.affiliation: Thoracic Oncology West China Hospital Sichuan University Chengdu China; State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Thoracic Oncology West China Hospital Sichuan University Chengdu China; State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China.
authors.forename: Wen
authors.initials: W
authors.lastname: Luo
authors.affiliation: Thoracic Oncology West China Hospital Sichuan University Chengdu China; State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China.
authors.forename: Renming
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Laboratory of Molecular Diagnosis of Cancer West China Hospital Sichuan University Chengdu China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China; Abdominal oncology West China Hospital Sichuan University Chengdu China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Thoracic Oncology West China Hospital Sichuan University Chengdu China; State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
keywords: Epidermal growth factor receptor; Rad51; mutation; non‐small cell lung cancer; radiosensitivity
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