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PMID: 9115210 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Basal cell carcinomas in mice overexpressing sonic hedgehog.

Science (New York, N.Y.) ·Vol. 276 ·No. 5313 ·1997-05-02 ·Pages 817-21

Oro AE, Higgins KM, Hu Z, Bonifas JM, Epstein EH, Scott MP

Abstract

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.

MeSH Terms

Animals Basal Cell Nevus Syndrome/genetics,metabolism,pathology Carcinoma, Basal Cell/genetics,metabolism,pathology Embryo, Mammalian Gene Expression Regulation, Neoplastic Hedgehog Proteins Humans Intracellular Signaling Peptides and Proteins Keratinocytes/metabolism Male Membrane Proteins/genetics,metabolism Mice Mice, SCID Mice, Transgenic Mutation Neoplasm Transplantation Patched Receptors Patched-1 Receptor Protein Biosynthesis Proteins/genetics,metabolism Receptors, Cell Surface Skin/pathology Skin Neoplasms/genetics,metabolism,pathology Skin Transplantation Trans-Activators

Chemicals

Hedgehog Proteins Intracellular Signaling Peptides and Proteins Membrane Proteins Patched Receptors Patched-1 Receptor Proteins Ptch1 protein, mouse Receptors, Cell Surface SHH protein, human Trans-Activators

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Oro A E

Howard Hughes Medical Institute, Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305-5427, USA.

Higgins K M

Hu Z

Bonifas J M

Epstein E H

Scott M P

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.276.5313.817

Published

1997-05-02

Pages

817-21

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

NIAMS NIH HHS · AR39959 · United States

External Links

PubMed source DOI: 10.1126/science.276.5313.817 View journal details

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Basal cell carcinomas in mice overexpressing sonic hedgehog.

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