TY - JOUR AB - Overexpression of epidermal growth factor (EGF) and urokinase plasminogen activator receptor (uPAR) have been observed in human gastric cancers. However, the interaction between EGF and uPAR in gastric cancer has not been well elucidated. In this study, we investigated the effect of EGF on uPAR expression and the underlying signal pathways in human gastric cancer AGS cells. EGF induced uPAR mRNA expression in a time- and concentration-dependent manner. EGF also induced uPAR promoter activity. In addition, EGF induced the activation of extracellular signal regulated kinase-1/2 (ERK-1/2) and P38 mitogen-activated protein kinase (MAPK) but not the activation of c-Jun amino terminal kinase. A specific inhibitor of MEK-1 (an upstream effector of ERK-1/2) and a dominant negative MEK-1 were able to suppress the EGF-induced uPAR promoter activity. Site-directed mutagenesis and electrophoretic mobility shift assays demonstrated that the binding sites of transcription factors, activator protein-1 (AP-1) and nuclear factor (NF)-κB, are involved in the EGF-induced uPAR transcription. Suppression of the EGF-induced uPAR promoter activity by the AP-1 decoy oligonuclotide, as well as expression vectors encoding mutated-type NF-κB-inducting kinase and I-κB, confirmed that the activation of AP-1 and NF-κB are essential for the EGF-induced uPAR upregulation. The AGS cells pretreated with EGF showed a remarkably enhanced invasiveness and this effect was partially abrogated by uPAR neutralizing antibodies and by the inhibitors of ERK-1/2, AP-1, and NF-κB. The above results suggest that EGF induces uPAR expression via ERK-1/2, AP-1, and NF-κB signaling pathways and, in turn, stimulates cell invasiveness in human gastric cancer AGS cells. AD - The Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University Medical School, Kwangju 501-190, Korea null AU - Baek,Min,K. AU - Kim,Mi,H. AU - Jang,Hee,J. AU - Park,Jung,S. AU - Chung,Ik,J. AU - Shin,Boo,A. AU - Ahn,Bong,W. AU - Jung,Young,D. DA - 2008/12/01 DO - 10.3892/or_00000181 EP - 1575 IS - 6 JO - Oncol Rep PY - 2008 SN - 1021-335X 1791-2431 SP - 1569 ST - EGF stimulates uPAR expression and cell invasiveness through ERK, AP-1, and NF-κB signaling in human gastric carcinoma cells T2 - Oncology Reports TI - EGF stimulates uPAR expression and cell invasiveness through ERK, AP-1, and NF-κB signaling in human gastric carcinoma cells UR - https://doi.org/10.3892/or_00000181 VL - 20 ER -