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.
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.
Authors: Salma K Jabbour; Terence M Williams; Mutlay Sayan; Eric D Miller; Jaffer A Ajani; Andrew C Chang; Norman Coleman; Wael El-Rifai; Michael Haddock; David Ilson; Daniel Jamorabo; Charles Kunos; Steven Lin; Geoffrey Liu; Pataje G Prasanna; Anil K Rustgi; Rosemary Wong; Bhadrasain Vikram; Mansoor M Ahmed Journal: J Natl Cancer Inst Date: 2021-06-01 Impact factor: 13.506