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

doi:10.1016/j.febslet.2005.12.093

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

294 Scopus citations

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)
Pages (from-to)	755-762
Number of pages	8
Journal	FEBS Letters
Volume	580
Issue number	3
DOIs	https://doi.org/10.1016/j.febslet.2005.12.093
State	Published - Feb 6 2006

Keywords

B7-H1
IFN-γ
IRF-1
JAK/STAT pathway

ASJC Scopus subject areas

Biochemistry
Biophysics
Molecular Biology

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10.1016/j.febslet.2005.12.093

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

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.",

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

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AU - Lee, Seung Jin

AU - Jang, Byeong Churl

AU - Lee, Soo Woong

AU - Yang, Young Il

AU - Suh, Seong Il

AU - Park, Yeong Min

AU - Oh, Sangtaek

AU - Shin, Jae Gook

AU - Yao, Sheng

AU - Chen, Lieping

AU - Choi, In Hak

PY - 2006/2/6

Y1 - 2006/2/6

N2 - 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.

AB - 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.

KW - B7-H1

KW - IFN-γ

KW - IRF-1

KW - JAK/STAT pathway

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

Abstract

Keywords

ASJC Scopus subject areas

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