PT  - JOURNAL ARTICLE
AU  - MAKOTO KIYOZUKA
AU  - TETSUO AKIMOTO
AU  - MIKA FUKUTOME
AU  - ATSUSHI MOTEGI
AU  - NORIO MITSUHASHI
TI  - Radiation-induced Dimer Formation of EGFR: Implications for the Radiosensitizing Effect of Cetuximab
DP  - 2013 Oct 01
TA  - Anticancer Research
PG  - 4337--4346
VI  - 33
IP  - 10
4099  - http://ar.iiarjournals.org/content/33/10/4337.short
4100  - http://ar.iiarjournals.org/content/33/10/4337.full
SO  - Anticancer Res2013 Oct 01; 33
AB  - 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.