TGFbeta is known to transactivate EGFR. However, the signaling component involved in this crosstalk has yet to be revealed. Here, we found that TGFbeta(1) phosphorylated EGFR in a dose-dependent manner in SCC13 and A431 cells, and it was not blocked by EGF-neutralizing antibody. H(2)O(2) was increased by TGFbeta(1) treatment in the same time-kinetics as EGFR activation. Pretreatment of N-acetyl cysteine abolished TGFbeta(1)-induced H(2)O(2) induction and EGFR activation. Direct treatment of H(2)O(2) phosphorylated EGFR and catalase inhibitor prolonged TGFbeta(1)-induced EGFR activation. These results show that TGFbeta(1) activates EGFR via an H(2)O(2)-dependent mechanism, which subsequently leads to the activation of Erk(1/2).
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