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

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-c-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.

• Authors: Junfang Deng, Yigang Qian, Lei Geng, Haiyang Xie, Yan Wang, Guoping Jiang, Lin Zhou, Ming Zhang, Shusen Zheng
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 137 Issue 2 Pg. 243-50 (Feb 2011) ISSN: 1432-1335 [Electronic] Germany
• PMID: 20390427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B7-1 Antigen
• PDCD1LG2 protein, human
• Programmed Cell Death 1 Ligand 2 Protein
• RNA, Messenger
• Interferon-gamma
• JAK2 protein, human
• Janus Kinase 2
• Proto-Oncogene Proteins c-akt
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 4

Topics

• Analysis of Variance
• B7-1 Antigen (genetics, metabolism)
• Blotting, Western
• Cell Line, Tumor
• Flow Cytometry
• Gene Expression Regulation, Neoplastic
• Humans
• Interferon-gamma (metabolism)
• Janus Kinase 2 (metabolism)
• MAP Kinase Kinase 4 (metabolism)
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Neoplasms (metabolism)
• Phosphorylation
• Programmed Cell Death 1 Ligand 2 Protein
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases (metabolism)