Retinoids block phenotypic cell transformation produced by sarcoma growth factor (original) (raw)

Nature volume 276, pages 272–274 (1978) Cite this article

Abstract

MURINE SARCOMA VIRUS (MSV)-transformed cells lack available receptors for epidermal growth factor (EGF)1,2. We have shown that this altered phenotype is the result of the endogenous production of growth factors by the MSV-trans-formed cells themselves. The major activity, isolated and purified from transformed cells, has been found in a 12,000-molecular weight peak and competed with EOF in an EGF-receptor-binding assay3. This growth factor, called sarcoma growth factor (SGF), stimulates cell division, causes normal cells to grow in soft agar and produces rapid, reversible morphological transformation of cells in monolayer culture3. There is no evidence that SGF acts as a complete carcinogen, producing permanent cell transformation; its properties resemble classical chemical promoters of carcinogenesis, like 12-_O_-tetradecanoylphorbol-13-acetate (TPA)4–6, the highly active component of croton oil. Whereas TPA is an exogenous plant derivative acting on an animal or a cell, SGF is an endogenous, virally induced growth promoter. In this respect it is interesting that retinoids (vitamin A and synthetic analogues)7 block the action in vivo of exogenous and endogenous promoters, preventing carcinogens from producing new tumours, but do not reverse the growth of many established tumours7–10. Retinoids prevent cancer of the lung7,11, skin9, bladder12 and mammary gland13 in experimental animals, block cell transformation induced by chemicals14 and radiation14,15 in culture, and reverse the anchorage-independent growth of transformed mouse fibroblasts16. If SGF is part of the natural tumour-promoting system and retinoids are part of the natural defence against that system, then one should be able to demonstrate a direct antagonism in cell culture. This, report establishes that this happens.

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References

  1. Todaro, G. J., De Larco, J. E. & Cohen, S. Nature 264, 26–31 (1976).
    Article ADS CAS Google Scholar
  2. Todaro, G. J., De Larco, J. E., Nissley, S. P. & Rechler, M. M. Nature 267, 526–528 (1977).
    Article ADS CAS Google Scholar
  3. De Larco, J. E. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. 75, 4001–4005 (1978).
    Article ADS CAS Google Scholar
  4. Boutwell, R. K. CRC Critical Revs Toxic. 2, 419–443 (1974).
    Article CAS Google Scholar
  5. Slaga, T. J., Sivak, A. & Boutwell, R. K. (eds) Mechanisms of Tumor Promotion and Carcinogenesis (Raven, New York, 1978).
  6. Weinstein, I. B. & Wigler, M. Nature 270, 659–660 (1977).
    Article ADS Google Scholar
  7. Sporn, M. B., Dunlop, N. M., Newton, D. L. & Smith, J. M. Fedn Proc. 35, 1332–1338 (1976).
    CAS Google Scholar
  8. Bollag, W. Cancer Chemother. Rep. 55, 53–55 (1971).
    CAS PubMed Google Scholar
  9. Bollage, W. Eur. J. Cancer 8, 689–693 (1972).
    Article Google Scholar
  10. Verma, A. K. & Boutwell, R. K. Cancer Res. 37, 2196–2201 (1977).
    CAS PubMed Google Scholar
  11. Saffiotti, U., Montesano, R., Sellakumar, A. R. & Borg, S. A. Cancer 20, 857–864 (1967).
    Article CAS Google Scholar
  12. Sporn, M. B. et al. Science 195, 487–489 (1977).
    Article ADS CAS Google Scholar
  13. Moon, R. C., Grubbs, C. J., Sporn, M. B. & Goodman, D. G. Nature 267, 620–621 (1977).
    Article ADS CAS Google Scholar
  14. Merriman, R. L. & Bertram, J. S. Cancer Res. (in the press).
  15. Harisiadis, L., Miller, R. C., Hall, E. J. & Borek, C. Nature 274, 486–487 (1978).
    Article ADS CAS Google Scholar
  16. Dion, L. D., Blalock, J. E. & Gifford, G. E. Expl Cell Res. (in the press).
  17. De Larco, J. E. & Todaro, G. J. J. cell. Physiol. 94, 335–342, (1978).
    Article CAS Google Scholar
  18. Miller, E. C. & Miller, J. A. in Chemical Mutagens-Principles and Methods for their Detection, Vol. 1 (ed. Hollaender, A.) 83–119 (Plenum, New York, 1971).
    Google Scholar
  19. Sivak, A. & Van Duuren, B. L. Science 157, 1443–1444 (1967).
    Article ADS CAS Google Scholar
  20. Van Duuren, B. L., Banerjee, S. & Witz, G. Chem.-Biol. Interactions 15, 233–245 (1976).
    Article CAS Google Scholar
  21. Lee, L. S. & Weinstein, I. B. Science (in the press).
  22. Hecker, E., Bresch, H. & Szczepanski, C. Angew. Chem. 3, 227 (1964).
    Article Google Scholar
  23. Van Duuren, B. L. & Orris, L. Cancer Res. 25, 1871–1875 (1965).
    CAS PubMed Google Scholar
  24. Huebner, R. J. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. 64, 1087–1094 (1969).
    Article ADS CAS Google Scholar
  25. Aaronson, S. A. & Stephenson, J. R. Biochim. biophys. Acta 458, 323–354 (1976).
    CAS PubMed Google Scholar
  26. Todaro, G. J., Callahan, R., Sherr, C. J., Benveniste, R. E. & De Larco, J. E. ICN-UCLA Symp. molec. Biol. 11 (Academic, New York, in the press).

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Authors and Affiliations

  1. National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20014
    GEORGE J. TODARO, JOSEPH E. DE LARCO & MICHAEL B. SPORN

Authors

  1. GEORGE J. TODARO
  2. JOSEPH E. DE LARCO
  3. MICHAEL B. SPORN

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TODARO, G., DE LARCO, J. & SPORN, M. Retinoids block phenotypic cell transformation produced by sarcoma growth factor.Nature 276, 272–274 (1978). https://doi.org/10.1038/276272a0

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