Transactivation of the epidermal growth factor receptor is involved in 12-O-tetradecanoylphorbol-13-acetate-induced signal transduction.

摘要: The mechanism of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion is still not well understood even though it thought to be related the protein kinase C/mitogen-activated kinase/AP-1 pathway. Recently, TPA was also found induce epidermal growth factor receptor (EGFR) activity. Here, we investigated whether EGFR a necessary component for TPA-induced signal transduction associated with promotion. We demonstrated that potent inhibitors EGFR, PD153035 and AG1478, blocked phosphorylation extracellular signal-regulated kinases (ERKs), AP-1 activity, cell transformation. Egfr gene deficiency ERK activity binding blocking ectodomain by monoclonal antibody depressed DNA use neutralizing heparin-binding EGF, one ligands ERKs. BB-94, inhibitor matrix metalloproteinases, which are activators shedding ligands, binding, transformation but had no effect on EGF-induced transduction. Anti-EGFR, anti-heparin-binding BB-94 each phosphorylation, only anti-EGFR could block phosphorylation. Based these results, conclude required mediating transactivation induced mediates promotion-related