Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity
作者： Klaus Dittmann , Claus Mayer , Hans-Peter Rodemann
DOI: 10.1016/J.RADONC.2005.06.022
关键词:
摘要: Abstract Background and purpose Inhibition of EGFR-function can induce radiosensitization in tumor cells. Purpose our investigation was to identify the possible molecular mechanism following treatment with anti-EGFR-antibody C225 (Cetuximab). Materials methods The effect on radiation response determined human cell lines bronchial carcinoma (A549) breast adenoma cells (MDA MB 231). effects after irradiation were analyzed applying western blotting, immune-precipitation kinase assays. Effects DNA-repair detected by quantification γ-H2AX positive foci 24 h irradiation. Results EGFR specific antibody induced A549 also MDA 231 Radiosensitization associated blockage radiation-induced transport into nucleus, immobilized complex DNA-dependent protein (DNA-PK) cytoplasm. As a consequence DNA-PK activation abolished, process that is essential for exposure. Likewise increased residual amount γ-H2AX-positive Conclusions Our results suggest activation—essential DNA repair—may be hampered specifically use C225. This radiosensitization.
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