論文 - 詳細
RRC ID | 68525 |
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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) |