Fig. 7. Proposed early signaling mechanism triggered in NB69 cells by the 50-Hz field stimulus. The EGF receptor (EGFR) activation, potentially mediated by prior activation of MMP-9, would trigger phosphorylation of p38 and ERK1/2 pathways, which are known to be involved in the proliferative response of NB69 to the MF. EGFR would also mediate the activation of JNK by the MF, though this signaling pathway may not be involved in the proliferative response to the MF, as indicated by previously published data. The results of the tests using chemical inhibitors show that both, the p38 pathway phosphorylation, which is mediated by free radicals (FR), and the FR-independent phosphorylation of the ERK1/2 pathway, have to take place simultaneously in order that the repeated response to the intermittent field exposure leads to the proliferative effect observed at 63 h of treatment (see Discussion for detailed explanation).