Epidermal Growth Factor Sensitizes Cells to Ionizing Radiation by Down-regulating Protein Mutated in Ataxia-Telangiectasia

摘要: Epidermal growth factor (EGF) has been reported to either sensitize or protect cells against ionizing radiation. We report here that EGF increases radiosensitivity in both human fibroblasts and lymphoblasts down-regulates ATM (mutated ataxia-telangiectasia (A-T)) the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). No further radiosensitization was observed A-T after pretreatment with EGF. The down-regulation occurs at transcriptional level. Concomitant ATM, DNA binding activity transcription Sp1 decreased. A causal relationship established between these observations by demonstrating up-regulation granulocyte/macrophage colony-stimulating rapidly reversed EGF-induced decrease restored normal levels. Failure radiosensitize EGF-treated same extent as for can be explained induction time post-irradiation. Although radiation damage activates cell cycle checkpoints, we have provided evidence first alteration amount response exposure. Taken together data support complex control function important repercussions targeting improve radiotherapeutic benefit.