Notch3 signaling initiates choroid plexus tumor formation
Notch3 signaling initiates choroid plexus tumor formation
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DOI：
10.1038/sj.onc.1209074
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发表时间：
2006-01-01
期刊：
影响因子：
8
通讯作者：
Eberhart, CG
中科院分区：
文献类型：
--
作者：
Dang, L;Fan, X;Eberhart, CG
Notch 3已经在大脑发育的背景下进行了研究，但它是否在脑肿瘤的形成中发挥作用尚不清楚。我们证明，引入组成型活性Notch 3到胚胎第9.5天小鼠的脑室周围细胞导致脉络丛肿瘤（CPT）的形成。83%的动物的第四脑室出现肿瘤，并与脑积水相关。它们在显微镜下与人类脉络丛乳头状瘤高度相似，持续增殖率为4- 6%。Notch通路活性的迹象也存在于人类脉络丛病变中，并且在乳头状瘤中的受体mRNA水平高于非肿瘤性脉络丛。Notch 2在一种情况下过表达约500倍，表明该途径在CPT中的作用可能不是Notch 3特异性的。我们的研究结果表明，激活的Notch 3可以作为一个癌基因在发育中的大脑，并连接Notch途径与人类CPT发病机制。
Notch3 has been studied in the context of brain development, but whether it plays a role in the formation of brain tumors is unclear. We demonstrate that the introduction of constitutively active Notch3 into periventricular cells of embryonic day 9.5 mice causes the formation of choroid plexus tumors (CPTs). Tumors arose in the fourth ventricles in 83% of animals and were associated with hydrocephalus. They were microscopically highly similar to choroid plexus papillomas in humans, with an ongoing proliferation rate of 4-6%. Signs of Notch pathway activity were also present in human choroid plexus lesions, and receptor mRNA levels in papillomas were elevated over those in non-neoplastic choroid plexus. Notch2 was overexpressed approximately 500-fold in one case, suggesting that the role of this pathway in CPTs may not be specific to Notch3. Our findings indicate that activated Notch3 can function as an oncogene in the developing brain, and link the Notch pathway to human CPT pathogenesis.