Cancer Immunology, Immunotherapy

, Volume 56, Issue 11, pp 1845–1852

STAT1-dependent and STAT1-independent gene expression in murine immune cells following stimulation with interferon-alpha

  • Jason M. Zimmerer
  • Gregory B. Lesinski
  • Michael D. Radmacher
  • Amy Ruppert
  • William E. CarsonIII
Original Article

DOI: 10.1007/s00262-007-0329-9

Cite this article as:
Zimmerer, J.M., Lesinski, G.B., Radmacher, M.D. et al. Cancer Immunol Immunother (2007) 56: 1845. doi:10.1007/s00262-007-0329-9

Abstract

Purpose

The precise molecular targets of interferon-alpha (IFN-α) therapy of melanoma are unknown but likely involve signal transducer and activator of transcription 1 (STAT1) signal transduction within host immune effector cells. We hypothesized that microarray analysis could be utilized to identify candidate molecular targets important for mediating the anti-tumor effect of exogenously administered IFN-α.

Experimental Methods

To identify the STAT1-dependent genes regulated by IFN-α, the gene expression profile of splenocytes from wild type (WT) and STAT1−/− mice was characterized.

Results

This analysis identified 30 genes that required STAT1 signal transduction for optimal expression in response to IFN-α (p < 0.001). These genes include granzyme b (Gzmb), interferon regulatory factor 7 (Irf7), Fas death domain-associated protein (Daxx), and lymphocyte antigen 6 complex, locus C (Ly6c). The expression of 20 genes was found to be suppressed in the presence of STAT1 including chemokine ligand 2 (Ccl2), Ccl5, and Ccl7. Nineteen genes were significantly upregulated in murine splenocytes following treatment with IFN-α regardless of the presence of STAT1 including CD86, lymphocyte antigen 6 complex, locus A (Ly6a), and Tap binding protein (Tapbp). The expression of representative IFN-responsive genes was confirmed at the transcriptional level by Real Time PCR.

Conclusion

This report is the first to demonstrate that STAT1-mediated signal transduction plays a major role in the transcriptional response of murine immune cells to IFNα.

Keywords

Interferon-alphaOligonucleotide microarray analysisSTAT1Immune cells

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jason M. Zimmerer
    • 1
    • 2
  • Gregory B. Lesinski
    • 2
  • Michael D. Radmacher
    • 3
  • Amy Ruppert
    • 3
  • William E. CarsonIII
    • 2
    • 4
  1. 1.Integrated Biological Sciences Graduate ProgramThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  2. 2.Human Cancer Genetics Program Department of Molecular Virology, Immunology, and Medical GeneticsThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  3. 3.Center for BiostastisticsThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  4. 4.Division of Surgical Oncology, Department of SurgeryThe Ohio State University Comprehensive Cancer CenterColumbusUSA