Sunburn and p53 in the onset of skin cancer

Annemarie Ziegler, Alan S. Jonason, David J. Leffellt, Jeffrey A. Simon, Harsh W. Sharma, Jonathan Kimmelman, Lee Remington, Tyler Jacks, Douglas E. Brash

Research output: Contribution to journalArticle

1254 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)773-776
Number of pages4
JournalNature
Volume372
Issue number6508
DOIs
StatePublished - Jan 1 1994

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    Ziegler, A., Jonason, A. S., Leffellt, D. J., Simon, J. A., Sharma, H. W., Kimmelman, J., Remington, L., Jacks, T., & Brash, D. E. (1994). Sunburn and p53 in the onset of skin cancer. Nature, 372(6508), 773-776. https://doi.org/10.1038/372773a0