Ultraviolet and ionizing radiation enhance the growth of BCCs and trichoblastomas in patched heterozygous knockout mice.
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.
Aszterbaum
M
M
Department of Dermatology, University of California San Francisco, Building 100, Room 269, 1001 Potrero Ave, San Francisco, California 94110, USA.
Epstein
J
J
Oro
A
A
Douglas
V
V
LeBoit
P E
PE
Scott
M P
MP
Epstein
E H
EH
D000818:Animals; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D006579:Heterozygote; D006801:Humans; D007763:Lac Operon; D019656:Loss of Heterozygosity; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018295:Neoplasms, Basal Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011839:Radiation, Ionizing; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D014466:Ultraviolet Rays; D000071676:Zinc Finger Protein GLI1
D008565:Membrane Proteins; D015513:Oncogene Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1