Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Keratinocytes blocked in phorbol ester-responsive early stage of terminal differentiation by sarcoma viruses

Nature volume 314, pages 459–462 (1985)Cite this article

Abstract

It has been suggested that the initiation step in mouse skin carcinogenesis involves an alteration in epidermal differentiation, as mouse basal keratinocytes exposed to initiators resist the arrest of cell growth that is normally associated with the induction of terminal differentiation by calcium ions1–3. The growth of epidermal basal cells infected by Kirsten (Ki) or Harvey (Ha) sarcoma viruses is, however, arrested in response to calcium ions, although the cells do not progress through their entire maturation programme when a functioning ras gene of those viruses is expressed4. If continuous proliferation in the differentiating cell layers is a requirement for tumour formation in skin3,5, the response of sarcoma virus-infected cells seems inconsistent with the suggestion that an activated ras gene is sufficient to initiate skin carcinogenesis6. We now show that sarcoma virus-infected keratinocytes, when induced to differentiate, are blocked at an early, reversible stage of maturation. Furthermore, the cells respond to phorbol ester tumour promoters by undergoing a phenotypic reversion to a less mature stage. These results suggest that activation of a ras gene can produce conditionally initiated cells, in which the full expression of tumorigenicity depends on exposure to tumour promoters.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kulesz-Martin, M., Koehler, B., Hennings, H. & Yuspa, S. H. Carcinogenesis 1, 995–1006 (1980).

    Article  CAS  Google Scholar 

  2. Yuspa, S. H. & Morgan, D. L. Nature 293, 72–74 (1981).

    Article  ADS  CAS  Google Scholar 

  3. Yuspa, S. H. in Cellular Interactions by Environmental Tumor Promoters (eds Fujiki, H., Hecker, E., Moore, R. E., Sugimura, T. & Weinstein, I. B.) 315–326 (Japan Scientific Societies Press, Tokyo).

  4. Yuspa, S. H., Vass, W. & Scolnick, E. Cancer Res. 43, 6021–6030 (1983).

    CAS  PubMed  Google Scholar 

  5. Yuspa, S. H., Hennings, H. & Lichti, U. J. supramolec. Struct. Cell Biochem. 17, 245–247 (1981).

    Article  CAS  Google Scholar 

  6. Balmain, A., Ramsden, M., Bowden, G. T. & Smith, J. Nature 307, 658–660 (1984).

    Article  ADS  CAS  Google Scholar 

  7. Hennings, H. et al. Cell 19, 245–254 (1980).

    Article  CAS  Google Scholar 

  8. Kulesz-Martin, M., Kilkenny, A. E., Holbrook, K. A., Digernes, V. & Yuspa, S. H. Carcinogenesis 4, 1367–1377 (1983).

    Article  CAS  Google Scholar 

  9. Balmain, A. & Pragnell, I. B. Nature 303, 72–74 (1983).

    Article  ADS  CAS  Google Scholar 

  10. Stanley, J. R., Hawley-Nelson, P., Yuspa, S. H., Shevach, E. M. & Katz, S. I. Cell 24, 897–903 (1981).

    Article  CAS  Google Scholar 

  11. Stanley, J. R., Woodley, D. T. & Katz, S. I. J. invest. Derm. 82, 108–111 (1984).

    Article  CAS  Google Scholar 

  12. Stanley, J. R., Koulu, C. & Thivolet, C. J. clin. Invest. 74, 313–320 (1984).

    Article  CAS  Google Scholar 

  13. Stanley, J. R. & Yuspa, S. H. J. Cell Biol. 96, 1809–1814 (1983).

    Article  CAS  Google Scholar 

  14. Hennings, H. & Holbrook, K. in Ions, Cell Proliferation and Cancer (eds Boynton, A. L., McKeehan, W. L. & Whitfield, J. F.) 499–516 (Academic Press, New York, 1982).

    Book  Google Scholar 

  15. Lichti, U., Patterson, E., Hennings, H. & Yuspa, S. H. J. cell. Physiol. 107, 261–270 (1981).

    Article  CAS  Google Scholar 

  16. Yuspa, S. H., Ben, T., Hennings, H. & Lichti, U. Cancer Res. 42, 2344–2349 (1982).

    CAS  PubMed  Google Scholar 

  17. Yuspa, S. H., Ben, T. & Hennings, H. Carcinogenesis 4, 1413–1418 (1983).

    Article  CAS  Google Scholar 

  18. Hennings, H., Steinert, P. & Buxman, M. M. Biochem. biophys. Res. Commun. 102, 739–745 (1981).

    Article  CAS  Google Scholar 

  19. Potten, C. S. Int. Rev. Cytol. 69, 271–318 (1981).

    Article  CAS  Google Scholar 

  20. Burns, F. J., Vanderlaan, M., Sivak, A. & Albert, R. E. Cancer Res. 36, 1422–1427 (1976).

    CAS  PubMed  Google Scholar 

  21. Scribner, J. D., Scribner, N. K., McKnight, B. & Mottet, N. K. Cancer Res. 43, 2034–2041 (1983).

    CAS  PubMed  Google Scholar 

  22. Kilkenny, A. E., Morgan, D., Spangler, E. F. & Yuspa, S. H. Cancer Res. (in the press).

  23. Hennings, H. et al. Nature 304, 67–69 (1983).

    Article  ADS  CAS  Google Scholar 

  24. Newbold, R. F. & Overell, R. W. Nature 304, 648–651 (1983).

    Article  ADS  CAS  Google Scholar 

  25. Land, H., Parada, L. F. & Weinberg, R. A. Nature 304, 596–602 (1983).

    Article  ADS  CAS  Google Scholar 

  26. Ruley, E. H. Nature 304, 602–606 (1983).

    Article  ADS  CAS  Google Scholar 

  27. Weissman, B. E. & Aaronson, S. A. Cell 32, 599–606 (1983).

    Article  CAS  Google Scholar 

  28. Higuche, M. & Yoshida, F. Analyt. Biochem. 77, 542–547 (1977).

    Article  Google Scholar 

  29. Toftgard, R., Roop, D. R. & Yuspa, S. H. Carcinogenesis (in the press).

Download references

Author information

Authors and Affiliations

  1. Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland, 20205, USA

    Stuart H. Yuspa, Anne E. Kilkenny & Ulrike Lichti

  2. Uniformed Services University of Health Sciences, Bethesda, Maryland, 20814, USA

    John Stanley

Authors
  1. Stuart H. Yuspa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne E. Kilkenny
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John Stanley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ulrike Lichti
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yuspa, S., Kilkenny, A., Stanley, J. et al. Keratinocytes blocked in phorbol ester-responsive early stage of terminal differentiation by sarcoma viruses. Nature 314, 459–462 (1985). https://doi.org/10.1038/314459a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/314459a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing