Transforming growth factorbeta(1) transactivates EGFR via an H(2)O(2)-dependent mechanism in squamous carcinoma cell line.
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).
Lee
EunAh
E
Department of Genetic Engineering, Musculoskeletal Bioorgan Center, Kyung Hee University, Yongin, Republic of Korea.
Yi
Jae Youn
JY
Chung
Eunkyung
E
Son
Youngsook
Y
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D020239:Receptor Cross-Talk; D015398:Signal Transduction / Q000502:physiology*; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D006861:Hydrogen Peroxide; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases