Journal
RADIOTHERAPY AND ONCOLOGY
Volume 101, Issue 1, Pages 147-151Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2011.05.046
Keywords
Double strand break repair; Epidermal growth factor receptor; Non-homologous end-joining; Homologous recombination; EGFR ligands; p53
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Purpose: The purpose of this study was to examine whether the epidermal growth factor receptor (EGFR) may be used as a general target to modulate DNA double strand break (DSB) repair in tumor cells. Material and methods: Experiments were performed with human tumor cell lines A549, H1299 and HeLa and primate cell line CV1, EGF, ARC and TGF alpha were used for EGFR activation, cetuximab or erlotinib for inhibition. Overall DSB repair was assessed by gamma H2AX/53BP1 co-immunostaining and non-homologous end-joining (NHEJ) and homologous recombination (HR) by using NHEJ and HR reporter cells: cell cycle distribution was determined by flow cytometry and protein expression by Western blot. Results: EGFR activation was found to stimulate overall DSB repair as well as NHEJ regardless of the ligand used. This stimulation was abolished when EGFR signaling was blocked. This regulation was found for all cell lines tested, irrespective of their p53 or K-Ras status. Stimulation and inhibition of EGFR were also found to affect HR. Conclusions: Regulation of DSB repair by EGFR involves both the NHEJ and HR pathway, and appears to occur in most tumor cell lines regardless of p53 and K-Ras mutation status. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 101 (2011) 147-151
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