EGR-1 Regulates Radiation-Induced Apoptosis in Human Head and Neck Squamous Cell Cancer

Objectives: (1) Investigate that early growth response-1 (EGR-1) expression is expressed in human head and neck squamous cancer (human HNSCC). (2) Evaluate whether EGR-1 affects radiation-induced apoptosis in human HNSCC and would thus serve as the proper prognostic biomolecular marker of radiation therapy. Methods: The protein expression of EGR-1 by immunohistochemistry was investigated in human HNSCC tissues. EGR-1 expression was evaluated at different time points after irradiation in human HNSCC cell lines. To evaluate the impact of EGR-1 knock-down on radiation-induced apoptosis of human HNSCC cell lines, cell apoptosis assays using small-interfering RNA were performed. Western blot analysis was used to assess alteration in apoptosis related protein expression after irradiation in human HNSCC cell lines. Results: EGR-1–positive immunoreactions were observed relative to adjacent mucosal tissue in 15 tissues (58.6%) of 28 human HNSCC tissues. After 5Gy and 8Gy irradiation, EGR-1 increased with peak activation at 2 hours. The cleaved caspase 3, cleaved caspase 7, and cleaved PARP were increased at 2 hours after irradiation. Proapoptotic protein Bax was increased at 2 hours after irradiation. EGR-1 knock-down cells displayed decreased radiation-induced apoptosis, compared with control cells in cell apoptosis assay. Cleaved caspase 3, cleaved caspase 7, cleaved PARP, and Bax activation was decreased by EGR-1 knock-down after irradiation. Conclusions: EGR-1 had abundant expression in human HNSCC tissue. EGR-1 knock-down decreased radiation-induced apoptosis through caspase 3, caspase, 7, PARP, and Bax. EGR-1 may play an important role in treatment response after radiation therapy in human HNSCC.