Ionizing radiation-induced mitogen-activated protein (MAP) kinase activation in DU145 prostate carcinoma cells: MAP kinase inhibition enhances radiation-induced cell killing and G2/M-phase arrest.

摘要: Hagan, M., Wang, L., Hanley, J. R., Park, S. and Dent, P. Ionizing Radiation-Induced Mitogen-Activated Protein (MAP) Kinase Activation in DU145 Prostate Carcinoma Cells: MAP Inhibition Enhances Cell Killing G2/M-Phase Arrest.These studies examine the role(s) played by mitogen-activated protein kinase (MAPK) pathway after exposure of prostate carcinoma cells to radiation. Radiation (2 Gy) was found cause both immediate primary (0–30 min) prolonged secondary activations (90–1440 MAPK pathway. These were abolished inhibition epidermal growth factor receptor (EGFR) function. The activation also addition a neutralizing monoclonal antibody against transforming α (TGFA). could be induced nonirradiated transfer medium from irradiated cultures. Neutralizing TGFA blocked this effect, indicating that radiation causes release cells. transient G2/M-phase arrest for up 24 h significantly increased ability apoptosis exposure. proliferate irradiation became dependent on signaling. When subjected single doses or fractionated exposure, continuous decreased clonogenic survival. Only small fraction cell killing accounted within first 96 h. Thus radiation-induced likely apoptotic nonapoptotic mechanisms. Collectively, our findings indicate disruption TGFA/EGFR/MAPK may represent strategy exploited manipulate survival irradiation.