Fig. 6.

EGF, TGFα, Amphiregulin- and pp60^Src -independent activation of EGFR signaling after chronic exposure to MCT. The levels of EGF in peripheral lung tissue lysates were measured by Western blot analysis (A, left panel) and ELISA (A, right panel) and no significant changes were observed between control rats or MCT-treated rats in the presence or absence of gefitinib. No changes were observed in the alternate EGFR receptor ligands TGFα (B) or amphiregulin (C). The activity of pp60^Src was also analyzed by Western blot analysis. Shown are the Western blot data from three different sets of rats. The levels of p-Y416pp60^Src were normalized to the level of pp60^Src. The activity of pp60^Src was not significantly different between groups (D). No significant differences were observed between groups in pp60^Src dependent activation of EGFR, as estimated by measuring the phosphorylation of Y845EGFR, a pp60^Src dependent site of EGFR, by Western blot analysis and normalization to the total level of EGFR in peripheral lung tissue (E). Shown are the Western blot data from two different sets of rats (E). No significant differences were observed in phosphorylation of Y845EGFR between control and the 28 days MCT group by Western blot analysis normalized to the total level of EGFR in peripheral lung tissue (F). The levels of p-Y416pp60^Src and total pp60^Src were significantly reduced between control and the 28 MCT group (F). Results are expressed as mean±SEM; N=4–7. P<0.05 vs. control group. †P<0.05 vs. MCT alone.