Transactivation of epidermal growth factor receptor by insulin-like growth factor 1 requires basal hydrogen peroxide

Insulin-like growth factor (IGF-1) plays an important role in prostate cancer development. Recent studies suggest that IGF-1 has mitogenic action through epidermal growth factor receptor (EGFR). However, the mechanism remains largely unknown. Here, we demonstrated in prostate cancer DU145 cells that IGF-1 induced EGFR transactivation, leading to ERK activation. Matrix metalloproteinase-mediated shedding of heparin-binding EGF is involved in this process. Antioxidants and catalase inhibited IGF-1-stimulated EGFR phosphorylation, indicating that H2O2 is required for EGFR activation. However, exogenous H2O2 did not activate EGFR or IGF-1R in DU145 cells. IGF-1 did not induced production of H2O2 in DU145 cells. Our results suggest that transactivation of EGFR by IGF-1 requires basal intracellular H2O2 in DU145 cells.