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

J Cancer Res Clin Oncol. 2011 Feb;137(2):243-50. doi: 10.1007/s00432-010-0876-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • B7-1 Antigen / genetics
  • B7-1 Antigen / 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


  • 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