Weiner Howard L, Bakst Richard, Hurlbert Marc S, Ruggiero Jason, Ahn Esther, Lee Wing Shing, Stephen Daniel, Zagzag David, Joyner Alexandra L, Turnbull Daniel H
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA.
Cancer Res. 2002 Nov 15;62(22):6385-9.
The Sonic hedgehog (Shh) signaling pathway plays a critical role in normal cerebellar development and has been implicated in medulloblastomas, common malignant childhood tumors of the cerebellum. To test whether Shh mis-expression is sufficient for medulloblastoma formation, we used ultrasound biomicroscopy-guided in utero injection of a Shh-expressing retrovirus into the cerebellum of 13.5-day mouse embryos to show that direct activation of the Shh pathway can lead to tumor formation. Significantly, medulloblastomas were observed in 76% of the mice infected with Shh-expressing retrovirus. Furthermore, contrary to recent suggestions that the Shh transcriptional target Gli1 plays a critical role in Shh-induced tumorigenesis, we found that medulloblastomas form in Gli1 null mutant mice. We have developed an efficient mouse model of medulloblastoma and shown that Gli1 is not required for tumorigenesis when Shh signaling is activated upstream in the pathway.
音猬因子（Shh）信号通路在正常小脑发育中起关键作用，且与髓母细胞瘤有关，髓母细胞瘤是儿童期常见的小脑恶性肿瘤。为了测试Shh的异常表达是否足以导致髓母细胞瘤的形成，我们利用超声生物显微镜引导，在子宫内将表达Shh的逆转录病毒注射到13.5天龄小鼠胚胎的小脑中，结果显示Shh信号通路的直接激活可导致肿瘤形成。值得注意的是，在感染了表达Shh逆转录病毒的小鼠中，76%出现了髓母细胞瘤。此外，与最近认为Shh转录靶点Gli1在Shh诱导的肿瘤发生中起关键作用的观点相反，我们发现Gli1基因敲除突变小鼠也会形成髓母细胞瘤。我们建立了一种高效的髓母细胞瘤小鼠模型，并表明当Shh信号通路在上游被激活时，肿瘤发生并不需要Gli1。
