| 지원과제 |
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| 저자명 |
Lee SJ, Jang BC, Lee SW, Yang YI, Suh SI, Park YM, Oh S, Shin JG, Yao S, Chen L, Choi IH. |
| 학회정보 |
FEBS Lett. 2006 Feb 6;580(3):755-62. |
| 제 목 |
Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). |
| LINK |
www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&d.. |
| 게시일 |
2006-09-22 10:54:04 |
| 년도 |
2006-International |
| 내용 |
Majority of cancer cells upregulate co-inhibitory molecule B7-H1 which confers resistance to anti-tumor immunity, allowing cancers to escape from host immune surveillance. We addressed the molecular mechanism underlying the regulation of cancer-associated B7-H1 expression in response to interferon-gamma (IFN-gamma). Using promoter constructs in luciferase assay, the region between 202 and 320 bp from the translational start site is responsible for B7-H1 expression. Electrophoretic mobility shift assay, site-directed mutagenesis and knockdown experiment using siRNA revealed that interferon regulatory factor-1 (IRF-1) is primarily responsible for the constitutive B7-H1 expression as well as for the IFN-gamma-mediated B7-H1 upregulation in a human lung cancer cell line A549. Additionally, AG490, a Janus activated kinase/signal transducer and activator of transcription inhibitor, greatly abolished the responsiveness of A549 cells to IFN-gamma by reducing the IRF-1 transcription. Our findings support a critical role of IRF-1 in the regulation of constitutive and IFN-gamma-induced expression of B7-H1 in cancer cells. |
