Activation of expression of hedgehog target genes in basal cell carcinomas
Activation of expression of hedgehog target genes in basal cell carcinomas
复制标题
DOI：
10.1046/j.1523-1747.2001.01315.x
复制
发表时间：
2001-05-01
影响因子：
6.5
通讯作者：
Epstein, EH
中科院分区：
文献类型：
--
作者：
Bonifas, JM;Pennypacker, S;Epstein, EH
Hedgehog信号通路基因的突变，尤其是PTC1和SMO，对于基底细胞癌的发生至关重要。基底细胞癌基因表达的研究不仅可以阐明hedgehog信号异常产生异常肿瘤细胞行为的机制，还可以提供人类体内hedgehog靶基因控制的数据。我们发现，与正常皮肤相比，基底细胞癌的 PTC1、GLI1、HIP、WNT2B 和 WNT5a mRNA 水平升高； c-MYC、c-FOS 和 WNT4 mRNA 水平降低； PTC2、GLI2、WNT7B、BMP2 和 4 的 mRNA 水平没有变化。这些发现表明，hedgehog 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。
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.