Thomas Stacey L, Deadwyler Gail D, Tang Jun, Stubbs Evan B, Muir David, Hiatt Kelly K, Clapp D Wade, De Vries George H
Research Service, Edward Hines Jr. V.A. Hospital, 5th Avenue and Roosevelt Road, Hines, IL 60141, USA.
Biochem Biophys Res Commun. 2006 Sep 29;348(3):971-80. doi: 10.1016/j.bbrc.2006.07.159. Epub 2006 Aug 2.
Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells.
源自1型神经纤维瘤病（NF1）患者外周神经鞘瘤的施万细胞缺乏神经纤维瘤蛋白，该蛋白含有一个GAP相关结构域（NF1-GRD）。缺乏神经纤维瘤蛋白的施万细胞具有增强的Ras激活、对某些生长刺激的增殖增加、增强的血管生成潜力以及改变的细胞形态。本研究检测了功能性NF1-GRD的表达是否能逆转来自良性和恶性外周神经鞘瘤的缺乏神经纤维瘤蛋白的施万细胞的转化表型。我们使用逆转录病毒转导重建了NF1-GRD，并检测了对细胞形态、生长潜力和血管生成潜力的影响。NF1-GRD重建导致形态学改变、缺乏神经纤维瘤蛋白的施万细胞中Ras激活降低16%-33%以及增殖减少53%。然而，NF1-GRD重建不足以降低细胞的体外血管生成潜力。本研究表明，NF1-GRD的重建至少可以部分逆转人NF1肿瘤来源的施万细胞的转化。
