Radiation-induced dimer formation of EGFR: implications for the radiosensitizing effect of cetuximab.

AIM The purpose of this study was to investigate whether radiation induces ligand-independent dimerization of epidermal growth factor receptor (EGFR) and explore the possible role of radiation-induced receptor dimerization in the radiosensitizing effect of cetuximab. MATERIALS AND METHODS The human vulvar squamous cell carcinoma cell line A431 was used. The dimerization and activation of EGFR were quantified using immunoprecipitation, a western blotting analysis, and a chemical cross-linking analysis with dithiobis-sulfosuccinimidyl propionate. RESULTS Irradiation at a dose of 2 Gy induced the autophosphorylation of EGFR. Consistent with autophosphorylation, a 360-kDa polypeptide, corresponding to the size of the EGFR dimer, was detected in addition to an EGFR monomer. Radiation also induced hetero-dimerization between EGFR and HER2/neu. Cetuximab combined with radiation inhibited radiation-induced autophosphorylation of EGFR, and inhibited radiation-induced homo-dimerization of EGFR. However, cetuximab incompletely inhibited radiation-induced hetero-dimerization between EGFR and HER2. CONCLUSION The results of this investigation suggest that radiation-induced homo- and/or hetero-dimerization between EGFR and/or HER2 might be involved in the radioresponse of cancer cells.