Neuregulin growth factors and their ErbB receptors form a potential signaling network for schwannoma tumorigenesis.
Neuregulin growth factors and their ErbB receptors form a potential signaling network for schwannoma tumorigenesis.
复制标题
神经调节蛋白生长因子及其 ErbB 受体形成神经鞘瘤肿瘤发生的潜在信号网络。
DOI：
10.1097/01.jnen.0000199575.93794.2f
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发表时间：
2006
影响因子：
3.2
通讯作者：
Carroll,StevenL
中科院分区：
文献类型：
--
作者：
Stonecypher,MarkS;Chaudhury,AbhikRay;Byer,StephanieJ;Carroll,StevenL
散发性和神经纤维瘤病2型相关的神经鞘瘤含有胶质生长因子（GGF）样活性，已被假设为促进肿瘤性雪旺细胞有丝分裂。目前尚不清楚这种GGF样活性是否是神经调节蛋白-1（NRG-1），一种表皮生长因子（EGF）相关分子，调节发育中的许旺细胞的增殖，存活和分化，相关因子NRG-2或另一种NRG/EGF配体。我们报道了神经鞘瘤内的肿瘤性神经鞘细胞过度表达来自II类和III类NRG-1亚家族的多种α和β跨膜前体。NRG-2 α和β转录物在一些肿瘤中类似地过表达。在其他8种已知的NRG/EGF配体中，只有肝素结合的EGF、表皮调节蛋白和TGFα在神经鞘瘤中可检测到。肿瘤性雪旺细胞几乎一致表达erbB 2和erbB 3，2种膜受体酪氨酸激酶介导NRG-1和NRG-2的作用。NRG受体erbB 4和EGF受体的表达在神经鞘瘤中也很明显，但更有限，仅发生在这些肿瘤的一个子集中。ErbB 2是所有erbB激酶的首选二聚化伴侣，在神经鞘瘤中被组成性磷酸化。这些观察结果表明，自分泌，旁分泌，和/或多分泌NRG-1/NRG-2信号促进神经鞘瘤的发病机制，这种信号通路可能是一个重要的治疗靶点神经鞘瘤。
Sporadic and neurofibromatosis type 2-associated schwannomas contain a glial growth factor (GGF)-like activity that has been hypothesized to promote neoplastic Schwann cell mitogenesis. It is not known whether this GGF-like activity is neuregulin-1 (NRG-1), an epidermal growth factor (EGF)-related molecule that regulates the proliferation, survival, and differentiation of developing Schwann cells, the related factor NRG-2, or another NRG/EGF ligand. We report that neoplastic Schwann cells within schwannomas overexpress multiple α and β transmembrane precursors from the class II and class III NRG-1 subfamilies. NRG-2 α and β transcripts are similarly overexpressed in some tumors. Of the other 8 known NRG/EGF ligands, only heparin-binding EGF, epiregulin, and TGFα are detectable in schwannomas. Neoplastic Schwann cells almost uniformly express erbB2 and erbB3, 2 membrane receptor tyrosine kinases mediating NRG-1 and NRG-2 action. Expression of the NRG receptor erbB4 and EGF receptor is also evident in schwannomas, but is more limited, occurring in only a subset of these tumors. ErbB2, the preferred dimerization partner for all erbB kinases, is constitutively phosphorylated in schwannomas. These observations suggest that autocrine, paracrine, and/or juxtacrine NRG-1/NRG-2 signaling promotes schwannoma pathogenesis and that this signaling pathway may be an important therapeutic target in schwannomas.