Bonifas J M, Pennypacker S, Chuang P T, McMahon A P, Williams M, Rosenthal A, De Sauvage F J, Epstein E H
Department of Dermatology, San Francisco General Hospital, California, USA.
J Invest Dermatol. 2001 May;116(5):739-42. doi: 10.1046/j.1523-1747.2001.01315.x.
Mutations in hedgehog signaling pathway genes, especially PTC1 and SMO, are pivotal to the development of basal cell carcinomas. The study of basal cell carcinoma gene expression not only may elucidate mechanisms by which hedgehog signaling abnormalities produce aberrant tumor cell behavior but also can provide data on in vivo hedgehog target gene control in humans. We have found, in comparison with normal skin, that basal cell carcinomas have increased levels of mRNA for PTC1, GLI1, HIP, WNT2B, and WNT5a; decreased levels of mRNA for c-MYC, c-FOS, and WNT4; and unchanged levels of mRNA for PTC2, GLI2, WNT7B, and BMP2 and 4. These findings suggest that mutations in hedgehog signaling pathway genes may exert both cell autonomous and indirect effects and indicate that basal cell carcinoma tumor cells have a phenotype that at least in some aspects resembles that of epidermal stem cells.
刺猬信号通路基因的突变，尤其是PTC1和SMO的突变，对基底细胞癌的发生发展至关重要。对基底细胞癌基因表达的研究不仅可以阐明刺猬信号异常产生异常肿瘤细胞行为的机制，还可以提供关于人类体内刺猬靶基因调控的数据。与正常皮肤相比，我们发现基底细胞癌中PTC1、GLI1、HIP、WNT2B和WNT5a的mRNA水平升高；c-MYC、c-FOS和WNT4的mRNA水平降低；而PTC2、GLI2、WNT7B以及BMP2和4的mRNA水平不变。这些发现表明，刺猬信号通路基因的突变可能发挥细胞自主和间接作用，并表明基底细胞癌肿瘤细胞具有至少在某些方面类似于表皮干细胞的表型。
