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Involvement of ERK and JNK pathways in IFN-γ-induced B7-DC expression on tumor cells

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Abstract

Purpose

B7-DC on tumor cells was demonstrated to promote tumor immunity; however, the precise mechanism responsible for the aberrant B7-DC expression remains unknown. Interferon gamma (IFN-γ) can induce B7-DC expression on macrophages and has been shown to regulate anti-tumor immunity by various mechanisms. This study was designed to investigate the relationship of IFN-γ and B7-DC on tumor cells and further explored the signal transduction pathways involved.

Methods

RT-PCR and flow cytometry were used for the analysis of B7-DC expression on various tumor cells. The phosphorylation of p38, ERK1/2, JNK, Akt, and JAK2 was determined by Western blot.

Results

IFN-γ markedly up-regulated B7-DC expression on various tumor cells and resulted in the phosphorylation of JAK2, JNK, ERK, p38, and Akt. Inhibition of ERK or JNK pathway significantly decreased IFN-γ-induced B7-DC expression, whereas inhibition of phosphorylation of Akt, p38, and JAK2 had very little effect on IFN-γ-induced B7-DC expression.

Conclusions

Our findings demonstrate that the pretreatment of tumor cells with IFN-γ enhances B7-DC expression through ERK and JNK pathways.

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Abbreviations

PD-1:

Programmed death 1

RT-PCR:

Reverse transcription-PCR

IFN-γ:

Interferon gamma

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Acknowledgments

This work was supported by Science and Technology Department of Zhejiang Province (No. 2006C33009) and National Key Technology R&D Program of China (No. 2008ZX10002-22) and Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health (No. KYJD09023).

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Authors and Affiliations

  1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China

    Junfang Deng, Yigang Qian, Lei Geng, Haiyang Xie, Yan Wang, Guoping Jiang, Lin Zhou, Ming Zhang & Shusen Zheng

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  1. Junfang Deng
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  2. Yigang Qian
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  3. Lei Geng
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  4. Haiyang Xie
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  5. Yan Wang
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  6. Guoping Jiang
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  7. Lin Zhou
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  8. Ming Zhang
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  9. Shusen Zheng
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Correspondence to Shusen Zheng.

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J. Deng and Y. Qian contributed equally to this work.

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Deng, J., Qian, Y., Geng, L. et al. Involvement of ERK and JNK pathways in IFN-γ-induced B7-DC expression on tumor cells. J Cancer Res Clin Oncol 137, 243–250 (2011). https://doi.org/10.1007/s00432-010-0876-x

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  • DOI: https://doi.org/10.1007/s00432-010-0876-x

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