Abstract
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-γ (IFN-γ). 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-γ-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-γ by reducing the IRF-1 transcription. Our findings support a critical role of IRF-1 in the regulation of constitutive and IFN-γ-induced expression of B7-H1 in cancer cells.
Original language | English (US) |
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Pages (from-to) | 755-762 |
Number of pages | 8 |
Journal | FEBS Letters |
Volume | 580 |
Issue number | 3 |
DOIs | |
State | Published - Feb 6 2006 |
Keywords
- B7-H1
- IFN-γ
- IRF-1
- JAK/STAT pathway
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology