[HTML][HTML] Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-γ-induced upregulation of B7-H1 (CD274)

SJ Lee, BC Jang, SW Lee, YI Yang, SI Suh, YM Park… - FEBS letters, 2006 - Elsevier
SJ Lee, BC Jang, SW Lee, YI Yang, SI Suh, YM Park, S Oh, JG Shin, S Yao, L Chen, IH Choi
FEBS letters, 2006Elsevier
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 320bp from the translational start site is responsible for B7-H1
expression. Electrophoretic mobility shift assay, site-directed mutagenesis and knockdown …
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 320bp 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.
Elsevier