Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene (original) (raw)

Nature volume 303, pages 72–74 (1983)Cite this article

Abstract

Several groups have shown that the malignant phenotype can be transferred to NIH/3T3 fibroblasts by incorporation of DNA isolated from tumour cell lines1–5. These studies have demonstrated that the transforming activity of DNA isolated from human bladder, lung and colon carcinoma cell lines is related to an alteration of the cellular homologues of the ras genes of Harvey or Kirsten murine sarcoma viruses6–11. It is, however, unclear what relevance these observations have to the multistage nature of tumorigenesis in vivo, in which several independent events are required in both humans12,13 and experimental animals14,15. The activation of a cellular oncogene in a defined experimental system for the progressive induction of solid tumours has not yet been demonstrated. We report here that high molecular weight DNA from transplanted squamous cell carcinomas induced by sequential treatment of mouse skin with initiators and promoters of carcinogenesis causes morphological transformation of NIH/3T3 fibroblasts at high frequency. The transforming properties are due to the transfer of an activated cellular homologue of the Harvey-ras (_ras_H) oncogene.

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

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

References

  1. Shih, C., Shilo, B., Goldfarb, M. P., Dannenberg, A. & Weinberg, R. A. Proc. natn. Acad. Sci. U.S.A. 76, 5714–5718 (1979).
    Article ADS CAS Google Scholar
  2. Cooper, G. M., Okenquist, S. & Silverman, L. Nature 284, 418–421 (1980).
    Article ADS CAS Google Scholar
  3. Shih, C., Padhy, L. C., Murray, M. J. & Weinberg, R. A. Nature 290, 261–264 (1981).
    Article ADS CAS Google Scholar
  4. Krontiris, T. G. & Cooper, G. M. Proc. natn. Acad. Sci. U.S.A. 78, 1181–1184 (1981).
    Article ADS CAS Google Scholar
  5. Perucho, M. et al. Cell 27, 467–476 (1981).
    Article CAS Google Scholar
  6. Santos, E., Tronick, S. R., Aaronson, S. A., Pulciani, S. & Barbacid, M. Nature 298, 343–347 (1982).
    Article ADS CAS Google Scholar
  7. Der, C. J., Krontiris, T. G. & Cooper, G. M. Proc. natn. Acad. Sci. U.S.A. 79, 3637–3640 (1982).
    Article ADS CAS Google Scholar
  8. Parada, L. F., Tabin, C. J., Shih, C. & Weinberg, R. A. Nature 297, 474–478 (1982).
    Article ADS CAS Google Scholar
  9. Reddy, E. P., Reynolds, R. K., Santos, E. & Barbacid, M. Nature 300, 149–152 (1982).
    Article ADS CAS Google Scholar
  10. Tabin, C. J. et al. Nature 300, 143–149 (1982).
    Article ADS CAS Google Scholar
  11. Taparowsky, E. et al. Nature 300, 762–765 (1982).
    Article ADS CAS Google Scholar
  12. Cairns, J. Nature 289, 353–357 (1981).
    Article ADS CAS Google Scholar
  13. Logan, J. & Cairns, J. Nature 300, 104–105 (1982).
    Article ADS CAS Google Scholar
  14. Hecker, E., Fusenig, N. E., Kunz, W., Marks, F. & Theilmann, H. W. (eds) Carcinogenesis Vol. 7 (RavenNew York, 1982).
  15. Boutwell, R. K. CRC crit. Rev. Tox. 2, 419–443 (1974).
    Article CAS Google Scholar
  16. Burns, F. J., Vanderlaan, M., Snyder, E. & Albert, R. E. in Carcinogenesis Vol. 2 (eds Slaga, T. J., Sivak, A. & Boutwell, R. K.) 91–96 (Raven, New York, 1978).
    Google Scholar
  17. Ellis, R. W. et al. J. Virol. 36, 408–420 (1980).
    CAS PubMed PubMed Central Google Scholar
  18. Pulciani, S. et al. Nature 300, 539–542 (1982).
    Article ADS CAS Google Scholar
  19. Murray, M. J. et al. Cell 25, 355–361 (1981).
    Article CAS Google Scholar
  20. Bubenik, J. et al. Int. J. Cancer 11, 765–773 (1973).
    Article CAS Google Scholar
  21. Marshall, C. J., Franks, L. M. & Carbonnel, A. W. J. natn. Cancer Inst. 58, 1743–1747 (1977).
    Article CAS Google Scholar
  22. Yuspa, S. H. & Morgan, D. L. Nature 293, 72–74 (1981).
    Article ADS CAS Google Scholar
  23. Shih, C., Weinberg, R. A. Cell 29, 161–169 (1982).
    Article CAS Google Scholar

Download references

Author information

Authors and Affiliations

  1. Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK
    Allan Balmain & Ian B. Pragnell

Authors

  1. Allan Balmain
    You can also search for this author inPubMed Google Scholar
  2. Ian B. Pragnell
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Balmain, A., Pragnell, I. Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene.Nature 303, 72–74 (1983). https://doi.org/10.1038/303072a0

Download citation

This article is cited by