In-Hye Jung, Je-Won Ryu and Sang-Wook Lee,
Asan Medical Center, South Korea
University of Ulsan College of Medicine, South Korea
Scientific Tracks Abstracts: Arch Can Res
Epidermal growth factor receptor (EGFR) signaling promotes cell proliferation and survival in several types of cancer. Here, however, we showed that EGF inhibits proliferation and promotes apoptosis in non-small cell lung cancer (NSCLC) cells. In A549 cells, EGF increased redox factor-1 (Ref-1) expression and the association of Ref-1 with zinc finger-containing transcriptional regulator (EGR1) via activation of p22phox, RAC1 and an NOX subunit. EGF increased p22phox and RAC1 expression through activation of purinergic receptors (P2Y). Elevated Ref-1/EGR1 levels increased phosphatase and PTEN levels, leading to inhibition of the Akt pathway. EGF-induced PTEN up-regulation increased apoptosis and autophagy-induced damage in A549 cells, whereas Ref-1 knockdown blocked EGF-induced PTEN up-regulation in an NOX -p22phox subunitindependent manner. In addition, p22phox knockdown restored EGF-induced effects, implying that changes in P2Y activity caused by EGF, which activates NOX via RAC1, influenced Ref-1-mediated redox regulation. Finally, EGF similarly attenuated cell proliferation and promoted autophagy and apoptosis in vivo in a xenograft model using A549 cells. These findings reveal that EGF-induced redox signaling is linked to Ref-1-induced death in NSCLC cells.
In-Hye Jung has completed her MSc from University of Ulsan College of Medicine. She is the Fellow in Department of Radiation Oncology of Asan Medical Center.
Spanish 
Chinese 
Russian 
German 
French 
Japanese 
Portuguese 
Hindi 