Basal cell carcinomas in mice overexpressing sonic hedgehog.
Mutations in the tumor suppressor gene PATCHED (PTC) are found in human patients with the basal cell nevus syndrome, a disease causing developmental defects and tumors, including basal cell carcinomas. Gene regulatory relationships defined in the fruit fly Drosophila suggest that overproduction of Sonic hedgehog (SHH), the ligand for PTC, will mimic loss of ptc function. It is shown here that transgenic mice overexpressing SHH in the skin develop many features of basal cell nevus syndrome, demonstrating that SHH is sufficient to induce basal cell carcinomas in mice. These data suggest that SHH may have a role in human tumorigenesis.
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Howard Hughes Medical Institute, Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305-5427, USA.
Higgins
K M
KM
Hu
Z
Z
Bonifas
J M
JM
Epstein
E H
EH
Scott
M P
MP
D000818:Animals; D001478:Basal Cell Nevus Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004622:Embryo, Mammalian; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009154:Mutation; D009368:Neoplasm Transplantation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016038:Skin Transplantation; D015534:Trans-Activators
D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D015534:Trans-Activators