Sunburn and p53 in the onset of skin cancer

Nature. 1994 Dec 22-29;372(6508):773-6. doi: 10.1038/372773a0.

Abstract

Squamous cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratinocytes; actinic keratosis (AK), spontaneously regressing keratinized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis. 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 SCCs were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / genetics*
  • DNA Mutational Analysis
  • Genes, p53*
  • Humans
  • Keratosis / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Neoplasms, Radiation-Induced / genetics*
  • Skin / radiation effects
  • Skin Neoplasms / etiology
  • Skin Neoplasms / genetics*
  • Sunburn* / genetics
  • Sunlight*
  • Ultraviolet Rays