Ultraviolet and Ionizing Radiation Enhance the Growth of BCCs and Trichoblastomas in Patched Heterozygous Knockout Mice

Nat Med. 1999 Nov;5(11):1285-91. doi: 10.1038/15242.

Abstract

Basal cell carcinomas, the commonest human skin cancers, consistently have abnormalities of the hedgehog signaling pathway and often have PTCH gene mutations. We report here that Ptch+/- mice develop primordial follicular neoplasms resembling human trichoblastomas, and that exposure to ultraviolet radiation or ionizing radiation results in an increase in the number and size of these tumors and a shift in their histologic features so that they more closely resemble human basal cell carcinoma. The mouse basal cell carcinomas and trichoblastoma-like tumors resemble human basal cell carcinomas in their loss of normal hemidesmosomal components, presence of p53 mutations, frequent loss of the normal remaining Ptch allele, and activation of hedgehog target gene transcription. The Ptch mutant mice provide the first mouse model, to our knowledge, of ultraviolet and ionizing radiation-induced basal cell carcinoma-like tumors, and also demonstrate that Ptch inactivation and hedgehog target gene activation are essential for basal cell carcinoma tumorigenesis.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Basal Cell / immunology
  • Carcinoma, Basal Cell / pathology*
  • Cell Division / drug effects*
  • Heterozygote*
  • Humans
  • Lac Operon
  • Loss of Heterozygosity
  • Membrane Proteins / genetics
  • Mice
  • Mice, Knockout
  • Neoplasms, Basal Cell / genetics
  • Neoplasms, Basal Cell / immunology
  • Neoplasms, Basal Cell / pathology*
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / immunology
  • Neoplasms, Radiation-Induced / pathology
  • Oncogene Proteins / genetics
  • Patched Receptors
  • Patched-1 Receptor
  • Radiation, Ionizing*
  • Receptors, Cell Surface
  • Trans-Activators
  • Transcription Factors / genetics
  • Ultraviolet Rays*
  • Zinc Finger Protein GLI1

Substances

  • Membrane Proteins
  • Oncogene Proteins
  • PTCH protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • Ptch1 protein, mouse
  • Receptors, Cell Surface
  • Trans-Activators
  • Transcription Factors
  • Zinc Finger Protein GLI1