RRC ID 68525
著者 Sato M, Tanaka T, Maemura K, Uchiyama T, Sato H, Maeno T, Suga T, Iso T, Ohyama Y, Arai M, Tamura J, Sakamoto H, Nagai R, Kurabayashi M.
タイトル The PAI-1 gene as a direct target of endothelial PAS domain protein-1 in adenocarcinoma A549 cells.
ジャーナル Am J Respir Cell Mol Biol
Abstract Endothelial PAS domain protein-1 (EPAS1) regulates transcription of the genes encoding erythropoietin and vascular endothelial growth factor, which are important for maintaining oxygen homeostasis. We have previously shown that plasminogen activator inhibitor-1 (PAI-1) gene expression is induced by hypoxia. In this study, we sought to determine whether PAI-1 gene expression is directly regulated by EPAS1 in cancer cells because activities of proteases and their inhibitors are tightly regulated for tumor invasion. Hypoxia increased the PAI-1 mRNA levels in human adenocarcinoma A549 cells. Overexpression of EPAS1 significantly increased the PAI-1 mRNA and protein levels. Transient transfection assays revealed that EPAS1 increased PAI-1 gene transcription through a sequence containing 5'-CACGTACA-3' located at -194 (we refer to it as site HREPAI-1) and GT-box located at -78. Electrophoretic gel mobility shift assays revealed that HREPAI-1 serves as a binding site for EPAS1, and Sp1 constitutively binds to GT-box. In conclusion, PAI-1 expression is induced by EPAS1 through HREPAI-1 and through an Sp1-binding site. These results indicate that the PAI-1 gene is a direct target of EPAS1 and suggest the role of EPAS1 and Sp1 in the hypoxic response of cancer cells.
巻・号 31(2)
ページ 209-15
公開日 2004-8-1
DOI 10.1165/rcmb.2003-0296OC
PII 2003-0296OC
PMID 15039136
MeSH Adenocarcinoma / metabolism* Adenocarcinoma / pathology Base Sequence Basic Helix-Loop-Helix Transcription Factors Cell Line, Tumor DNA Primers DNA-Binding Proteins / metabolism Enzyme-Linked Immunosorbent Assay Humans Protein Binding Protein Serine-Threonine Kinases / metabolism* Proteins / genetics* Sp1 Transcription Factor / metabolism Sp1 Transcription Factor / physiology Sp3 Transcription Factor Transcription Factors / metabolism
IF 5.373
リソース情報
ヒト・動物細胞 A549(RCB0098)