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The v-Ki-ras Oncogene Up-Regulates Major Histocompatibility Class II Antigen Expression in Early-Passage Fibroblasts

  • R. L. Darley
  • A. G. Morris
Part of the NATO ASI Series book series (NSSA, volume 220)

Abstract

A long-term goal of oncogene research is to understand how proto-oncogene products affect cell physiology and how their function is subverted in their mutationally activated form. Oncogene products are widely regarded as playing a role in cell growth and control, but they may also contribute to the malignant phenotype by influencing cell functions other than growth. The effect of oncogenes on the expression of antigens of the major histocompatibility complex (MHC) is one such example. These molecules are of particular interest because both experimental (1–4) and clinical evidence (5,6) suggests their expression on cancer cells can correlate with the ability of the host to reject the tumour. The function of these molecules is integral to the process of immune recognition, and it is thought that their expression decreases the tumorigen-icity of cancer cells as a result of immunosurveillance by T cells. Modulation of MHC antigen expression by oncogenes, therefore, has a dual significance: not only may it provide information concerning the interaction of oncogenes with intracellular signalling pathways, but the outcome of this interaction may have indirect consequences for tumour growth.

Keywords

Major Histocompatibility Complex Major Histocompatibility Complex Class Antigen Expression Fibroblast Line Major Histocompatibility Class 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    W. J. Bateman, R. Fiera, N. Matthews, A. G. Morris, Inducibility of class II major histocompatibility complex antigens by interferon-γ is associated with reduced tumorigenicity in C3H mouse fibroblasts transformed by v-Ki-ras, J. Exp. Med., 173: 193–196 (1991)PubMedCrossRefGoogle Scholar
  2. 2.
    R. F. L. James, S. Edwards, K. M. Hui, P.D. Bassett, F. Grosveld, The effect of class II gene transfection on the tumorigenicity of the H-2K-negative mouse leukaemia cell line K36.16, Immunology, 72: 213–218 (1991)PubMedGoogle Scholar
  3. 3.
    S. O-Rosenberg, A. Thakur, V. Clements, Rejection of mouse sarcoma cells after transfection of MHC class II genes, J. Immunol., 144: 4068–4071 (1990)Google Scholar
  4. 4.
    G. J. Hammerling, D. Klar, W. Pulm, F. Momburg, G. Moldenhauer, The influence of major histocompatibility complex class I antigens on tumour growth and metastasis, Biochim. Biophys. Acta, 907:245–259 (1987)Google Scholar
  5. 5.
    T. P. Miller, S. M. Lippman, C. M. Spier, D. J. Slymen, T. M. Grogan, HLA-DR (Ia) antigen immune phenotype predicts outcome for patients with diffuse large cell lymphoma, J. Clin. Invest., 82: 370–372 (1988)PubMedCrossRefGoogle Scholar
  6. 6.
    F. Esterban, F. Ruiz-Cabello, A. Concha, M. Perezayala, J. Sanchezrosas, F. Garrido, HLA-DR expression is associated with excellent prognosis in squamous cell carcinoma of the larynx, Clin. Exp. Metastasis, 8: 319–328 (1990)CrossRefGoogle Scholar
  7. 7.
    P. Giacomini, P. B. Fisher, G. J. Duigou, R. Gambari, P. G. Natali, Regulation of class II MHC gene expression by interferons, Anticancer Research, 8: 1153–1162 (1988)PubMedGoogle Scholar
  8. 8.
    C. R. Hume, R. S. Accolla, J. S. Lee, Defective HLA class II expression in a regulatory mutant is partially complemented by activated ras oncogenes, Proc. Natl. Acad. Sci. USA, 84: 8603–8607 (1987)PubMedCrossRefGoogle Scholar
  9. 9.
    A. P. Albino, A. N. Houghton, M. Eisinger, J. S. Lee, R. R. S. Kantor, A. I. Oliff, L. J. Old, Class II histocompatibility antigen expression in human melanocytes transformed by Harvey murine sarcoma virus (Ha-MSV) and Kirsten MSV retroviruses, J. Exp. Med., 164: 1710–1722 (1986)PubMedCrossRefGoogle Scholar
  10. 10.
    D. J. Maudsley, A. G. Morris, Kirsten murine sarcoma virus abolishes interferon-γ-induced class II but not class I major histocompatibility antigen expression in a murine fibroblast line, J. Exp. Med., 167: 706–711 (1988)PubMedCrossRefGoogle Scholar
  11. 11.
    A. Balmain, M. Ramsden, G. T. Bowden, J. Smith, Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas, Nature (Lond.), 307: 658–660 (1984)CrossRefGoogle Scholar
  12. 12.
    K. Brown, M. Quintanilla, M. Ramsden, I. B. Kerr, S. Young, A. Balmain, v-ras genes from Harvey and Balb murine sarcoma viruses can act as initiators of two-stage mouse skin carcinogenesis, Cell, 46: 447–456 (1986)PubMedCrossRefGoogle Scholar
  13. 13.
    E. Liu, B. Hjelle, R. Morgan, F. Hecht, J. M. Bishop, Mutations of the Kirsten-ras proto-oncogene in human preleukaemia, Nature (Lond.), 330: 186–188 (1987)CrossRefGoogle Scholar
  14. 14.
    A. G. Morris, G. Ward, Production of recombinant interferons by expression in heterologous mammalian cells, in: Interferons and Lymphokines: a practical approach, M. Clemens, A. G. Morris, A. Gearing, editors. IRL Press: Oxford, 61–71 (1987)Google Scholar
  15. 15.
    G. J. Atkins, M. D. Johnston, L. M. Westmacott, D. C. Burke, Induction of interferon in chick cells by temperature-sensitive mutants of Sindbis virus, J. Gen. Virol., 25: 381 (1974)PubMedCrossRefGoogle Scholar
  16. 16.
    M. E. F. Smith, J. G. Bodmer, A. P. Kelly, J. Trowsdale, S. C. Kirkland, W. F. Bodmer, Variation in HLA expression on tumours, in: Cold Spring Harbor Symposia on Quantitative Biology, vol. LIV Cold Spring Harbor Laboratory Press (1989)Google Scholar
  17. 17.
    F. Momburg, A. Ziegler, J. Harpprecht, P. Moller, G. Moldenhauer, G. J. Hammerling, Selective loss of HLA-A or HLA-B antigen expression in colon carcinoma, J. Immunol., 142: 352–358 (1989)PubMedGoogle Scholar
  18. 18.
    J. L. Bos, E. R. Fearon, S. R. Hamilton, M. Verlaan-de Vries, J. H. van Boom, A. J. van der Eb, B. Vogelstein, Prevalence of ras gene mutations in human colorectal cancers, Nature (Lond.), 327: 293–297 (1987)CrossRefGoogle Scholar
  19. 19.
    M. R. Oliva, T. Cabrera, J. Esquivias, M. Perez-Ayala, M. Redondo, F. Ruiz-Cabello, F. Garrido, K-ras mutations (codon 12) are not involved in down-regulation of MHC class I genes in colon carcinomas, Int. J. Cancer, 46: 426–431 (1990)PubMedCrossRefGoogle Scholar
  20. 20.
    P. L. Kaplan, M. Anderson, B. Ozanne, Transforming growth factor(s) production enables cells to grow in the absence of serum: an autocrine system, Proc. Natl. Acad. Sci. USA, 79: 485–489 (1982)PubMedCrossRefGoogle Scholar
  21. 21.
    R. D. Owen, M. C. Ostrowski, Transcriptional activation of a conserved sequence element by ras requires a nuclear factor distinct from c-fos or c-jun, Proc. Natl. Acad. Sci. USA, 87: 3866–3870 (1990)PubMedCrossRefGoogle Scholar
  22. 22.
    C. W. Czarniecki, H. H. Chiu, G. H. W. Wong, S. M. McCabe, M. A. Palladino, Transforming growth factor-β modulates the expression of class II histocompatibility antigens on human cells, J. Immunol., 140: 4217–4223 (1988)PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • R. L. Darley
    • 1
  • A. G. Morris
    • 1
  1. 1.Cancer Research Campaign Interferon and Cellular Immunity Research Group, Department of Biological SciencesUniversity of WarwickCoventryUK

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