p53 protects against skin cancer induction by UV-B radiation

Oncogene. 1999 Jul 22;18(29):4247-53. doi: 10.1038/sj.onc.1202789.

Abstract

To assess the role of the p53 tumor suppressor gene in skin carcinogenesis by UV radiation, mice constitutively lacking one or both copies of the functional p53 gene were compared to wild-type mice for their susceptibility to UV carcinogenesis. Heterozygous mice showed greatly increased susceptibility to skin cancer induction, and homozygous p53 knockout mice were even more susceptible. Accelerated tumor development in the heterozygotes was not associated with loss of the remaining wild-type allele of p53, as reported for tumors induced by other carcinogens, but in many cases was associated with UV-induced mutations in p53. Tumors arose on the ears and dorsal skin of mice of all three genotypes, and homozygous knockout mice also developed ocular tumors, mainly melanomas. Skin tumors in the p53 knockout mice were predominately squamous cell carcinomas and were associated with premalignant lesions resembling actinic keratoses, whereas those in the heterozygous and wild-type mice were mainly sarcomas. These results demonstrate the importance of p53 in protecting against UV-induced cancers, particularly in the eye and epidermis.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / prevention & control*
  • Codon / genetics
  • Crosses, Genetic
  • DNA, Neoplasm / genetics
  • Epidermis / metabolism
  • Epidermis / radiation effects*
  • Exons / genetics
  • Eye Neoplasms / etiology
  • Eye Neoplasms / genetics
  • Eye Neoplasms / prevention & control*
  • Gene Dosage
  • Genes, p53*
  • Genetic Predisposition to Disease
  • Genotype
  • Keratosis / etiology
  • Keratosis / genetics
  • Melanoma, Experimental / etiology
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / prevention & control*
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Precancerous Conditions / etiology
  • Precancerous Conditions / genetics
  • Radiation Tolerance / genetics*
  • Sarcoma, Experimental / etiology
  • Sarcoma, Experimental / genetics
  • Sarcoma, Experimental / prevention & control*
  • Skin Neoplasms / etiology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / prevention & control*
  • Specific Pathogen-Free Organisms
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / physiology*
  • Ultraviolet Rays / adverse effects*

Substances

  • Codon
  • DNA, Neoplasm
  • Tumor Suppressor Protein p53