Modulation of SOCS protein expression influences the interferon responsiveness of human melanoma cells

Gregory B Lesinski1, Jason M Zimmerer, Melanie Kreiner

  • 1Department of Surgery Arthur G, James Cancer Hospital and Richard J, Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.

BMC Cancer
|April 20, 2010
PubMed
Abstract

Insights

Suppressors of cytokine signaling (SOCS) proteins are present in melanoma cells and impact interferon signaling. Modulating SOCS expression influences melanoma cell response to interferon therapy, offering potential therapeutic strategies.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Interferons (IFNs) regulate melanoma cell growth and are used in cancer therapy.
  • Suppressors of cytokine signaling (SOCS) are negative regulators of IFN signaling.
  • The role of SOCS in mediating IFN-resistance in human melanoma remains unclear.

Purpose of the Study:

  • To investigate the role of SOCS1 and SOCS3 in mediating interferon-resistance in human melanoma cells.
  • To determine the effect of SOCS protein modulation on melanoma cell responsiveness to IFNs.

Main Methods:

  • Immunoblot analysis to assess SOCS1 and SOCS3 expression in melanoma cell lines and melanocytes.
  • Over-expression of SOCS proteins using retroviral vectors and inhibition using siRNA.
  • Flow cytometry to measure STAT1 phosphorylation and Real-Time PCR for IFN-stimulated gene expression.

Main Results:

  • SOCS1 and SOCS3 proteins are expressed in human melanoma cells and their expression is enhanced by IFN-alpha and IFN-gamma stimulation.
  • Over-expression of SOCS proteins inhibited STAT1 phosphorylation and IFN-stimulated gene expression.
  • Inhibition of SOCS proteins using siRNA enhanced melanoma cell responsiveness to IFN stimulation.

Conclusions:

  • SOCS proteins are expressed in human melanoma and influence melanoma cell response to IFN-alpha and IFN-gamma.
  • Modulating SOCS expression presents a potential strategy to enhance the efficacy of interferon-based therapies for melanoma.

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