Tumor suppressor mutations and growth factor signaling in the pathogenesis of NF1-associated peripheral nerve sheath tumors: II. The role of dysregulated growth factor signaling.
Tumor suppressor mutations and growth factor signaling in the pathogenesis of NF1-associated peripheral nerve sheath tumors: II. The role of dysregulated growth factor signaling.
复制标题
NF1相关周围神经鞘瘤发病机制中的抑癌基因突变和生长因子信号传导：II。
DOI：
10.1093/jnen/64.1.1
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发表时间：
2005
影响因子：
3.2
通讯作者：
Stonecypher,MarkS
中科院分区：
文献类型：
--
作者：
Carroll,StevenL;Stonecypher,MarkS
1型神经纤维瘤病（NF1）是影响神经系统的最常见遗传性疾病之一，患有NF1的患者会发生多发性神经纤维瘤，这些神经纤维瘤可以转化为恶性外周神经鞘瘤（MPNST）。对人类肿瘤和新开发的转基因小鼠模型的研究表明，雪旺细胞是神经纤维瘤和MPNST中的主要肿瘤细胞类型，这些外周神经鞘肿瘤的发展涉及多个肿瘤抑制基因的突变。然而，人们普遍认为，肿瘤抑制基因突变本身不足以诱导周围神经鞘肿瘤的形成，而失调的生长因子信号传导与这些突变协同作用，促进神经纤维瘤和MPNST肿瘤发生。在这篇综述的第一部分，我们讨论了一些发现，这些发现表明肿瘤性雪旺细胞中NF 1肿瘤抑制基因功能的丧失是神经纤维瘤形成的关键早期步骤，并且从神经纤维瘤进展到MPNST与其他肿瘤抑制基因的异常有关，包括p53、INK4A和p27 kip 1。在本综述的第二部分中，我们考虑了特定生长因子和生长因子受体信号失调促进神经纤维瘤和MPNSTs中肿瘤性雪旺细胞增殖、迁移和存活的证据。
Patients with neurofibromatosis type 1 (NF1), one of the most common genetic disease affecting the nervous system, develop multiple neurofibromas that can transform into aggressive sarcomas known as malignant peripheral nerve sheath tumors (MPNSTs). Studies of human tumors and newly developed transgenic mouse models indicate that Schwann cells are the primary neoplastic cell type in neurofibromas and MPNSTs and that development of these peripheral nerve sheath tumors involves mutations of multiple tumor suppressor genes. However, it is widely held that tumor suppressor mutations alone are not sufficient to induce peripheral nerve sheath tumor formation and that dysregulated growth factor signaling cooperates with these mutations to promote neurofibroma and MPNST tumorigenesis. In Part I of this review, we discussed findings demonstrating that a loss ofNF1tumor suppressor gene function in neoplastic Schwann cells is a key early step in neurofibroma formation and that progression from neurofibroma to MPNST is associated with abnormalities of additional tumor suppressor genes, including p53,INK4A,andp27kip1. In Part II of this review, we consider evidence that dysregulated signaling by specific growth factors and growth factor receptors promotes the proliferation, migration, and survival of neoplastic Schwann cells in neurofibromas and MPNSTs.