Chen Bo-Yie, Liu Jer-Yuh, Chang Han-Hsin, Chang Chin-Pao, Lo Wei-Yuh, Kuo Wu-Hsien, Yang Chi-Rei, Lin David P C
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan.
Biochem Biophys Res Commun. 2007 Jun 15;357(4):1084-9. doi: 10.1016/j.bbrc.2007.04.091. Epub 2007 Apr 20.
The role of Hedgehog signaling in human basal cell hyperplasia formation and its progressing towards tumorigenesis was investigated. Hedgehog signaling members including PTCH1, GLI1, GLI2, and GLI3 were found co-localized with p63 expression in most hyperplastic basal cells, but rarely in normal basal cells, suggesting Hedgehog involvement in basal cell hyperplasia formation. Both CK-14 and CK-8 markers were found co-localized in the majority of hyperplastic basal cells, but relatively few in the normal basal cells, indicating a Hedgehog-promoted transitory differentiation. Furthermore, CK-14 and PTCH1 were found co-localized with CD44 in the hyerplastic basal cells, in a way similar to the CD44 co-localization with PTCH1 and GLI1 in the cancer cells. Together, the present study indicated Hedgehog involvement in forming basal cell hyperplasia and its progressing towards cancer, presumably by transforming the normal basal stem cells into the cancer stem cells where persistent Hedgehog activation might be mandatory for tumorigenesis.
研究了刺猬信号通路在人类基底细胞增生形成及其向肿瘤发生进展过程中的作用。在大多数增生性基底细胞中发现刺猬信号通路成员,包括PTCH1、GLI1、GLI2和GLI3,与p63表达共定位,但在正常基底细胞中很少见,这表明刺猬信号通路参与基底细胞增生的形成。发现CK-14和CK-8标志物在大多数增生性基底细胞中共定位,但在正常基底细胞中相对较少,表明刺猬信号通路促进了短暂分化。此外,在增生性基底细胞中发现CK-14和PTCH1与CD44共定位,其方式类似于癌细胞中CD44与PTCH1和GLI1的共定位。总之,本研究表明刺猬信号通路参与基底细胞增生的形成及其向癌症的进展,可能是通过将正常基底干细胞转化为癌症干细胞,而持续的刺猬信号通路激活可能是肿瘤发生所必需的。