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:

Phorbol ester and Epstein—Barr virus dependent transformation of normal primary human skin epithelial cells

Abstract

Substantial evidence has implicated Epstein–Barr virus (EBV) in the aetiology of two human neoplasms, nasopharyngeal carcinoma (NPC) and Burkitt's lymphoma1,2. This is supported by the presence of high antibody titres to EBV early antigen and virus capsid antigen3,4, as well as antibody to two viral-associated enzymes, DNase and DNA polymerase5,6. Patients with NPC, particularly the undifferentiated form, are commonly found to have EBV DNA in the tumour2. Ito and others7–10 have presented strong epidemio-logical evidence that phorbol esters are related to the unusual geographic distribution of NPC in southeastern regions of China. There appears to be a close link between the widespread EBV infection of the Asian population and the distinct regional distribution in China of plants that produce diterpene ester11. Naturally occurring phorbol esters are produced by plants of the Euphor-biaceae and Thymelaeaceae, which are used as traditional herbal medicines12. Although it has been established that EBV can infect epithelial cells isolated from NPC as well as certain normal epithelial cells13–15, there has been no in vitro evidence that EBV induces neoplastic transformation in normal human epithelial cells with or without exposure to phorbol esters. We report here evidence that transformation of normal human epithelial cells results from exposure to infectious EBV and that transformation is dependent on the presence of phorbol esters.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Epstein, M. A., Achong, B. G. & Barr, Y. M. Lancet i, 702–703 (1964).

    Article  Google Scholar 

  2. Zur Hausen, H. et al. Nature 228, 1056–1058 (1970).

    Article  ADS  CAS  Google Scholar 

  3. Henle, W. et al. J. natn. Cancer Inst. 44, 225–231 (1970).

    CAS  Google Scholar 

  4. Henle, G., Henle, W. & Klein, G. Int. J. Cancer 8, 272–282 (1971).

    Article  CAS  Google Scholar 

  5. Cheng, Y. C., Chen, J. Y., Glaser, R. & Henle, W. Proc. natn. Acad. Sci. U.S.A. 77, 6162–6165 (1980).

    Article  ADS  CAS  Google Scholar 

  6. Chiou, J. F., Li, J. K. K. & Cheng, Y. C. Proc. natn. Acad. Sci. U.S.A. 82, 5728–5731 (1985).

    Article  ADS  CAS  Google Scholar 

  7. Hirayama, T. & Ito, Y. Prev. Med. 10, 614–622 (1981).

    Article  CAS  Google Scholar 

  8. Ito, Y., Kawanishi, M., Harayama, T. & Takabayashi, S. Cancer Lett. 12, 175–180 (1981).

    Article  CAS  Google Scholar 

  9. Mizuno, F. et al. Cancer Lett. 19, 199–205 (1983).

    Article  CAS  Google Scholar 

  10. Zeng, Y. et al. Cancer Lett. 23, 53–59 (1984).

    Article  CAS  Google Scholar 

  11. Fedder, M. & Gonzalez, M. F. Am. J. Med. 79, 365–369 (1985).

    Article  CAS  Google Scholar 

  12. Duke, J. A. & Ayensu, E. S. in Medicinal Plants of China 300–314 (Reference Publications, Algonac, Michigan, 1985).

    Google Scholar 

  13. Glaser, R., de-The, G., Lenoir, G. & Ho, J. H. C. Proc. natn. Acad. Sci. U.S.A. 73, 960–963 (1976).

    Article  ADS  CAS  Google Scholar 

  14. Glaser, R. et al. J. natn. Cancer Inst. 64, 1085–1090 (1980).

    Article  CAS  Google Scholar 

  15. Sixbey, J. W., Nedrud, J. G., Raab-Traub, N., Hanes, R. A. & Pagano, J. S. New Engl. J. Med. 310, 1225–1230 (1984).

    Article  CAS  Google Scholar 

  16. Stoerker, J., Yajima, Y. & Glaser, R. Int. J. Cancer 30, 385–392 (1982).

    Article  CAS  Google Scholar 

  17. Lehman, T. A., Noyes, I. & Milo, G. E. Tissue Culture Association Manual (in the press).

  18. Hamburger, A. & Salmon, S. E. Science 197, 461–463 (1977).

    Article  ADS  CAS  Google Scholar 

  19. Farber, E. Cancer Res. 44, 4217–4223 (1984).

    CAS  PubMed  Google Scholar 

  20. Shi, S.-R. et al. Am. J. Path. 117, 53–63 (1984).

    CAS  PubMed  Google Scholar 

  21. Young, L. S., Clark, D., Sixbey, J. W. & Rickinson, A. B. Lancet i, 240–242 (1986).

    Article  Google Scholar 

  22. Graessman, A., Wolf, H. & Bornkamm, G. W. Proc. natn. Acad. Sci. U.S.A. 77, 433–436 (1980).

    Article  ADS  Google Scholar 

  23. Stoerker, J., Parris, D., Yajima, Y. & Glaser, R. Proc. natn. Acad. Sci. U.S.A. 78, 5852–5855 (1981).

    Article  ADS  CAS  Google Scholar 

  24. Stevenson, M., Volsky, B., Hedenskog, M. & Volsky, D. J. Science 233, 980–984 (1986).

    Article  ADS  CAS  Google Scholar 

  25. Shanmugaratnam, K. & Sabin, L. H. International Histological Classification of Tumors No. 19 (World Health Organization, Geneva, 1978).

    Google Scholar 

  26. Andersson-Anvret, M., Forsby, N., Klein, G. & Henle, W. Int. J. Cancer 20, 486–491 (1977).

    Article  CAS  Google Scholar 

  27. Neel, H. B. III et al. Laryngoscope 90, 1981–1990 (1980).

    Article  Google Scholar 

  28. Micheau, C., de-The, G., Schwaab, G. & Lengrand, D. in Nasopharyngeal Carcinoma: Current Concepts (eds Prasad, U. et al.) 65–70 (University of Malaya, Kuala Lumpur, 1983).

    Google Scholar 

  29. Kitano, Y. & Hata, S. Arch. derm. Forsch. 245, 203–210 (1972).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tomei, L., Noyes, I., Blocker, D. et al. Phorbol ester and Epstein—Barr virus dependent transformation of normal primary human skin epithelial cells. Nature 329, 73–75 (1987). https://doi.org/10.1038/329073a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/329073a0

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

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