Brain Tumor Biology Unit-CIFA, University of Navarra School of Sciences, Pamplona, Spain.
Cancer Lett. 2011 Nov 28;310(2):222-31. doi: 10.1016/j.canlet.2011.07.005. Epub 2011 Jul 18.
Sonic hedgehog (Hh) developmental pathway deregulation has been proven to play an essential role in several malignancies as neuroblastoma. We found that Hh signaling is active in neuroblastoma, as most pathway components, including GLI1, were expressed in cell lines and tumor samples. Furthermore, SHH ligand expression was found in cell lines and tumors, and GLI1 up-regulation was achieved in response to SHH treatment, suggesting an autocrine mechanism of aberrant activation. A decrease of proliferation and tumorigenic potential, as well as increased apoptosis and a dramatic decrease in the percentage of CD15+ cell population were produced upon Hh inhibition by cyclopamine.
Sonic hedgehog (Hh) 发育途径失调已被证明在多种恶性肿瘤中起重要作用，如神经母细胞瘤。我们发现 Hh 信号在神经母细胞瘤中是活跃的，因为大多数途径成分，包括 GLI1，在细胞系和肿瘤样本中表达。此外，在细胞系和肿瘤中发现了 SHH 配体的表达，并且在受到 SHH 处理时 GLI1 上调，表明存在异常激活的自分泌机制。通过 cyclopamine 抑制 Hh，可导致增殖和致瘤潜能降低，凋亡增加，以及 CD15+细胞群比例显著下降。
