In-Hye Jung
University of Ulsan College of Medicine, Seoul, South Korea
Title: EGF induces paradoxical growth arresting via the up-regulation of PTEN by activating Ref-1/Egr-1 in human NSCLC cells
Biography
Biography: In-Hye Jung
Abstract
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 fi nger-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 eff ects, implying that changes in P2Y activity caused by EGF, which activates NOX via RAC1, infl uenced 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. Th ese fi ndings reveal that EGF-induced redox signaling is linked to Ref-1-induced death in NSCLC cells.