BASAL-CELL CARCINOMAS IN MICE OVEREXPRESSING SONIC HEDGEHOG

Mutations in the tumor suppressor gene PATCHED (PTC) are found in huma n patients with the basal cell nevus syndrome, a disease causing devel opmental defects and tumors, including basal cell carcinomas. Gene reg ulatory relationships defined in the fruit fly Drosophila suggest that overproduction of Sonic hedgehog (SHH), the ligand for PTC, will mimi c loss of ptc function. It is shown here that transgenic mice overexpr essing SHH in the skin develop many features of basal cell nevus syndr ome, demonstrating that SHH is sufficient to induce basal cell carcino mas in mice. These data suggest that SHH may have a role in human tumo rigenesis.