Abstract
SQUAMOUS cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratin-ocytes; actinic keratosis (AK), spontaneously regressing keratin-ized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis1–3. To understand how sunlight acts as a carcinogen, we determined the stage at which sunlight mutates the p53 tumour-suppressor gene and identified a function for p53 in skin. The p53 mutations induced by ultraviolet radiation and found in >90% of human SCCs4,5 were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells6, apoptotic keratinocytes generated by overexposure to ultraviolet. Skin thus appears to possess a p53-dependent 'guardian-of-the-tissue' response to DNA damage which aborts precancerous cells. If this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p53-mutated cell into the AK. Sunlight can act twice: as tumour initiator and tumour promoter.
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
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Gilchrest, B. A. Skin and Aging Processes (CRC Press, Boca Raton, 1984).
Schwartz, R. A. & Stoll, H. L. in Dermatology in General Medicine (eds Fitzpatrick, T. B., Eisen, A. Z., Wolff, K., Freedberg, I. M. & Austen, K. F.) 804–807 (McGraw-Hill, New York, 1993).
Campbell, C., Quinn, A. G., Ro, Y.-S., Angus, B. & Rees, J. L. J. Invest. Dermatol. 100, 746–748 (1993).
Brash, D. E. et al. Proc. natn. Acad. Sci. U.S.A. 88, 10124–10128 (1991).
Ziegler, A. et al. Proc. natn. Acad. Sci. USA 90, 4216–4220 (1993).
Danno, K. & Horio, T. Photochem. Photobiol. 45, 683–690 (1987).
Hutchinson, F. Mutat. Res. 309, 11–15 (1994).
Lowe, S., Schmitt, E. M., Smith, S. W., Osborne, B. A. & Jacks, T. Nature 362, 847–849 (1993).
Clarke, A. R. et al. Nature 362, 849–852 (1993).
Rosario, R., Mark, G. J., Parrish, J. A. & Mihm, M. C. Br. J. Dermat. 101, 299–308 (1979).
Vogelstein, B. & Kinzler, K. W. Cell 70, 523–526 (1992).
Fisher, D. E. Cell 78, 539–542 (1994).
Campbell, C., Quinn, A. G., Angus, B., Farr, P. M. & Rees, J. L. Cancer Res. 53, 2697–2699 (1993).
Epstein, J. H., Fukuyama, K. & Fye, K. Photochem. Photobiol. 12, 57–65 (1970).
Ley, R. D. & Applegate, L. A. J. Invest. Dermat. 85, 365–367 (1985).
Kemp, C. J., Donehower, L. A., Bradley, A. & Balmain, A. Cell 74, 813–822 (1993).
Cairns, J. Nature 255, 197–200 (1975).
Potter, V. R. Cancer Res. 44, 2733–2736 (1984).
Epstein, J. H. & Epstein, W. L. J. Invest. Dermat. 39, 455–460 (1962).
Cerutti, P. A. Science 227, 375–381 (1985).
Burns, F. J., Vanderlaan, M., Sivak, A. & Albert, R. E. Cancer Res. 36, 1422–1427 (1976).
Moolgavkar, S. H. & Knudson, A. G. J. natn. Cancer Inst. 66, 1037–1052 (1981).
Urbach, F., Rose, D. B. & Bonnem, M. in Environment and Cancer 355–371 (Williams and Wilkins, Baltimore, 1972).
Kricker, A., Armstrong, B. K., English, D. R. & Heenan, P. J. Int. J. Cancer 48, 650–662 (1991).
Marks, R., Foley, P., Goodman, G., Hage, B. H. & Selwood, T. S. Br. J. Dermat. 115, 649–655 (1986).
Marks, R., Jolley, D., Lectsas, S. & Foley, P. Med. J. Austral. 152, 62–66 (1990).
Greenblatt, M. S., Bennett, W. P., Hollstein, M. & Harris, C. C. Cancer Res. 54, 4855–4878 (1994).
Glass, A. G. & Hoover, R. N. J. Am. med. Assoc. 262, 2097–2100 (1989).
Singer-Sam, J., LeBon, J. M., Daj, A. & Riggs, A. D. PCR Meth. Appl. 1, 160–163 (1992).
Gavrieli, Y., Sherman, Y. & Ben-Sasson, S. A. J. Cell Biol. 119, 493–501 (1992).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ziegler, A., Jonason, A., Leffellt, D. et al. Sunburn and p53 in the onset of skin cancer. Nature 372, 773–776 (1994). https://doi.org/10.1038/372773a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/372773a0
This article is cited by
-
Encapsulation of ultraviolet filter into cationic polystyrene particles via miniemulsion polymerization with poly(vinyl alcohol)
Colloid and Polymer Science (2024)
-
The journey from melanocytes to melanoma
Nature Reviews Cancer (2023)
-
Advances in cutaneous squamous cell carcinoma
Nature Reviews Cancer (2023)
-
NCOA3, a new player in melanoma susceptibility and a therapeutic target
Cancer Gene Therapy (2022)
-
p21CIP1 controls the squamous differentiation response to replication stress
Oncogene (2021)
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.