Abstract
Ionizing radiation (IR) has been shown to activate epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). EGFR activation by IR initiates the Ras/Raf/ERK signaling cascade, stimulates cell proliferation, and leads cells to be resistant to IR. The molecular mechanisms underlying IR-induced activation of EGFR are not clear. We have previously reported that IR-induced ERK1/2 activation involves EGFR through a Src-dependent pathway that is distinct from EGFR ligand activation. In the present study, we investigated the effects of carbon-beam on activities of ERK1/2, EGFR, and Src as indicated by their tyrosine phosphorylation and effects of AG1478 on them using human breast cancer cell line MDA-MB-468. Exposure of MDA-MB-468 cells to carbon-beam caused biphasic activation of ERK as indicated by its phosphorylation at Thr202/Tyr204. AG1478 inhibited carbon-beam-induced ERK1/2 activation. Carbon-beam did not induced EGFR autophosphorylation at Tyr992, Tyr1045 and Tyr1068 or Src-dependent EGFR phosphorylation at Tyr845. Src became activated as indicated by phosphorylation at Tyr416. These data suggest that carbon-beam activates ERK1/2 through transactivation of EGFR.
