Oro A E, Higgins K M, Hu Z, Bonifas J M, Epstein E H, Scott M P
Howard Hughes Medical Institute, Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305-5427, USA.
Science. 1997 May 2;276(5313):817-21. doi: 10.1126/science.276.5313.817.
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.
在患有基底细胞痣综合征的人类患者中发现了肿瘤抑制基因PTCH（patched，PTCH基因）的突变，该疾病会导致发育缺陷和肿瘤，包括基底细胞癌。果蝇中定义的基因调控关系表明，PTCH的配体音猬因子（Sonic hedgehog，SHH）过量产生会模拟ptc功能丧失。本文表明，在皮肤中过表达SHH的转基因小鼠出现了基底细胞痣综合征的许多特征，这表明SHH足以在小鼠中诱导基底细胞癌。这些数据表明SHH可能在人类肿瘤发生中起作用。
