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

Seung Jin Lee, Byeong Churl Jang, Soo Woong Lee, Young Il Yang, Seong Il Suh, Yeong Min Park, Sangtaek Oh, Jae Gook Shin, Sheng Yao, Lieping Chen, In Hak Choi

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)755-762
Number of pages8
JournalFEBS Letters
Volume580
Issue number3
DOIs
StatePublished - Feb 6 2006

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Keywords

  • B7-H1
  • IFN-γ
  • IRF-1
  • JAK/STAT pathway

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Lee, S. J., Jang, B. C., Lee, S. W., Yang, Y. I., Suh, S. I., Park, Y. M., Oh, S., Shin, J. G., Yao, S., Chen, L., & Choi, I. H. (2006). Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-γ-induced upregulation of B7-H1 (CD274). FEBS Letters, 580(3), 755-762. https://doi.org/10.1016/j.febslet.2005.12.093