Schwann cells from neurofibromin deficient mice exhibit activation of p21ras, inhibition of cell proliferation and morphological changes.
Schwann cells from neurofibromin deficient mice exhibit activation of p21ras, inhibition of cell proliferation and morphological changes.
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发表时间：
1995-07
期刊：
影响因子：
8
通讯作者：
Haesun A Kim;T. Rosenbaum;Marchionni Ma;N. Ratner;D. Je
中科院分区：
文献类型：
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作者：
Haesun A Kim;T. Rosenbaum;Marchionni Ma;N. Ratner;D. Je
雪旺细胞被认为是异常的1型神经纤维瘤病（NF 1），并有助于形成良性和恶性肿瘤在这种疾病。为了测试NF 1基因产物神经纤维蛋白作为雪旺细胞中的Ras-GT3活化蛋白的作用，并研究神经纤维蛋白的缺失对雪旺细胞增殖的影响，我们从具有靶向破坏NF 1的小鼠中分离雪旺细胞。这些神经纤维蛋白缺陷细胞的性质与神经纤维蛋白水平正常的表达v-ras的大鼠雪旺细胞的性质惊人地相似。相似之处包括：生长抑制，表现为对胶质生长因子2（GGF 2）的反应导致细胞分裂减少和神经元接触减少;形态学变化，如出现精细加工过程;以及Ras-GTP水平升高。此外，在神经纤维蛋白缺陷的雪旺细胞中的Ras-GTP水平响应于GGF 2处理而持续升高。与这些结果相反，将v-ras引入神经鞘瘤细胞系（RN 22）导致细胞转化。我们的结论是，神经纤维蛋白作为一个主要的调节Ras-GTP在雪旺细胞的功能，然而，在NF 1本身的突变是不太可能解释的增生观察到的雪旺细胞肿瘤NF 1疾病。
Schwann cells are thought to be abnormal in type 1 neurofibromatosis (NF1) and to contribute to the formation of benign and malignant tumors in this disease. To test the role of the NF1 gene product neurofibromin as a Ras-GTPase activating protein in Schwann cells, and to study the effect of the loss of neurofibromin on Schwann cell proliferation, we isolated Schwann cells from mice with targeted disruption of NF1. The properties of these neurofibromin deficient cells were strikingly similar to those of v-ras expressing rat Schwann cells with normal levels of neurofibromin. The similarities included: growth inhibition, noted as a decrease in cell division in response to glial growth factor 2 (GGF2) and of neuronal contact; morphological changes such as the appearance of elaborated processes; and elevated levels of Ras-GTP. Furthermore, Ras-GTP levels in the neurofibromin deficient Schwann cells were consistently elevated in response to GGF2 treatment. In contrast to these results, introduction of v-ras into a Schwannoma cell line (RN22) led to cell transformation. We conclude that neurofibromin functions as a major regulator of Ras-GTP in Schwann cells; however, mutation in NF1 by itself is unlikely to explain the hyperplasia observed in Schwann cell tumors in NF1 disease.