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Related Experiment Videos

Sequential changes in MHC antigen expression induced by the v-Ki-ras oncogene

R L Darley1, A G Morris

  • 1Department of Biological Sciences, University of Warwick, Coventry, UK.

Cancer Immunology, Immunotherapy : CII
|November 1, 1993
PubMed
Summary

Activated ras oncogenes initially boost major histocompatibility complex (MHC) class II antigen expression in cells. However, prolonged cell passage leads to decreased MHC antigen inducibility, potentially mediated by transforming growth factor beta (TGF-β).

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Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • The v-Ki-ras oncogene activates the ras gene, influencing cellular functions.
  • Major histocompatibility complex (MHC) antigens play a crucial role in immune responses.
  • Understanding oncogene effects on MHC expression is vital for cancer immunology.

Purpose of the Study:

  • To investigate how an activated ras gene affects the expression of MHC antigens in cell lines.
  • To determine the impact of ras transformation on the inducibility of MHC class I and class II antigens by interferon gamma (IFN-γ).

Main Methods:

  • Transformation of early-passage cell lines with the v-Ki-ras oncogene.
  • Analysis of MHC class I and class II antigen expression following interferon gamma (IFN-γ) induction.

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  • Coculture experiments and conditioned media analysis to identify soluble factors.

    • Main Results:

    • Ras transformation initially enhanced MHC class II antigen expression upon IFN-γ induction.
    • Ras transformation decreased sensitivity to IFN-γ for MHC class I antigen induction.
    • Subsequent cell passage led to attenuated inducibility of both MHC class I and class II antigens.
    • A transferable factor, potentially transforming growth factor beta (TGF-β), was implicated in modulating MHC antigen expression.

    Conclusions:

    • Activated ras oncogenes induce complex phenotypic changes in MHC antigen expression.
    • TGF-β may act as a soluble factor that downregulates MHC antigen inducibility in ras-transformed cells.
    • These findings suggest a mechanism by which tumors might evade immune surveillance through altered MHC expression.