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Transcriptional program associated with IFN-alpha response of renal cell carcinoma

Debendranath Banerjee1, Rajendrakumar S V Chadalavada, Veronique Bourdon

  • 1Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
|March 18, 2006
PubMed

Insights

Interferon-alpha (IFN-alpha) therapy benefits some metastatic renal cell carcinoma (RCC) patients. Gene expression reveals sensitive RCC cells upregulate apoptosis, while resistant cells promote survival and proliferation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Metastatic renal cell carcinoma (RCC) is largely resistant to conventional therapies.
  • A subset of patients (10-20%) shows favorable responses to interferon-alpha (IFN-alpha) treatment.
  • The molecular mechanisms underlying differential responses to IFN-alpha in RCC remain unclear.

Purpose of the Study:

  • To investigate the global gene expression profiles of IFN-alpha-sensitive and -resistant RCC cell lines.
  • To identify molecular differences associated with response versus resistance to IFN-alpha therapy.
  • To elucidate the role of apoptosis and cell survival pathways in IFN-alpha treatment outcomes.

Main Methods:

  • Global gene expression analysis using high-density oligonucleotide arrays.
  • Comparison of gene expression patterns in six sensitive and six resistant RCC cell lines.
  • Time-course gene expression analysis following interferon-alpha2b treatment in selected sensitive and resistant cell lines.

Main Results:

  • No significant baseline gene expression differences were observed between sensitive and resistant cell lines without IFN-alpha.
  • IFN-alpha treatment modulated hundreds of transcripts in both cell types, with many shared targets related to antiviral and immunomodulatory functions.
  • Sensitive cells showed upregulation of pro-apoptotic transcripts, whereas resistant cells exhibited induction of survival/proliferation transcripts and suppression of apoptotic molecules.

Conclusions:

  • The response to IFN-alpha in RCC is determined by the balance between apoptosis and cell survival/proliferation pathways, not single gene alterations.
  • Gene expression patterns in these critical pathways dictate individual tumor sensitivity or resistance to IFN-alpha therapy.
  • This finding provides a molecular basis for understanding differential therapeutic outcomes in metastatic RCC treated with IFN-alpha.

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