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Inhibition of interferon-gamma antiviral and antiproliferative activities by ras oncogene expression

M Gariglio1, G Gribaudo, A Franco

  • 1Institute of Microbiology, University of Turin Medical School, Italy.

Journal of the National Cancer Institute
|July 5, 1989
PubMed

Insights

Ras oncogene activation impairs cell response to interferon-gamma (IFN-gamma) but not interferon-alpha (IFN-alpha). This suggests ras oncogenes affect intracellular signaling pathways downstream of IFN-gamma receptor binding.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Ras oncogenes are key regulators of cell signaling pathways.
  • Interferons (IFNs) are crucial for antiviral and antiproliferative responses.
  • Dysregulation of ras and IFN signaling is implicated in cancer development.

Purpose of the Study:

  • To investigate the impact of ras oncogene activation on cellular responses to IFN-gamma and IFN-alpha.
  • To determine if ras transformation affects IFN-induced antiviral, antiproliferative, or immune-modulatory functions.

Main Methods:

  • NIH 3T3 murine fibroblasts were transfected with K-, Ha-, or N-ras oncogenes.
  • Transformed and normal cells were treated with IFN-gamma or IFN-alpha for 24 hours.
  • Cellular responses were assessed by measuring virus replication, DNA synthesis ([3H]thymidine incorporation), 2',5'-oligoadenylate synthetase activity, and class I antigen expression.

Main Results:

  • Ras-transformed cells exhibited significantly reduced sensitivity to IFN-gamma's antiviral and antiproliferative effects.
  • IFN-gamma-induced 2',5'-oligoadenylate synthetase activation was abolished in ras-transformed cells.
  • Class I antigen induction by IFN-gamma was partially impaired, while responses to IFN-alpha remained intact.
  • Ras transformation did not affect IFN-gamma receptor binding affinity.

Conclusions:

  • Ras oncogene activation differentially impairs IFN-gamma signaling pathways downstream of receptor binding.
  • These findings highlight a potential mechanism by which ras oncogenes contribute to immune evasion in cancer.
  • Targeting ras-mediated signaling could restore IFN sensitivity in cancer cells.

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