Reduced expression of schwannomin/merlin in human sporadic meningiomas
Reduced expression of schwannomin/merlin in human sporadic meningiomas
复制标题
DOI：
10.1097/00006123-199703000-00031
复制
发表时间：
1997-03-01
期刊：
影响因子：
4.8
通讯作者：
Golubic, M
中科院分区：
文献类型：
--
作者：
Lee, JH;Sundaram, V;Golubic, M
目的：2型神经纤维瘤病基因在散发性脑膜瘤中经常发生突变。 2 型神经纤维瘤病基因的蛋白质产物称为 schwannomin 或 merlin。据我们所知，其在脑膜瘤来源的软脑膜细胞中的表达以及脑膜瘤中突变形式的特征尚未被研究。 方法：使用两种特异性抗体进行免疫印迹和免疫沉淀实验来测定兔和人脑组织中雪旺诺明/梅林的大小和亚细胞分布，并建立人软脑膜LTAg2B细胞。使用免疫印迹法测定 14 例人类散发性脑膜瘤中 schwannomin/merlin 的表达水平。 结果：两种抗体均检测到约 66 kDa 的蛋白质，该蛋白质主要在大脑的 Triton X-100 不溶部分和 LTAg2B 细胞中表达。与人脑、LTAg2B 细胞和其余 6 个脑膜瘤中的表达水平相比，8 个肿瘤 (57%) 中的 schwannomin/merlin 水平严重降低。具有正常雪旺诺明/默林表达的所有六个肿瘤均为脑膜瘤型。相比之下，所有其他组织学类型和一种具有沙粒体的脑膜皮瘤肿瘤均缺乏 66-kDa 雪旺诺蛋白/merlin。尽管导致过早终止密码子的无义突变在脑膜瘤的神经纤维瘤病 2 型基因中很常见，但我们在分析的肿瘤中没有发现截短的 schwannomin/merlin 形式的证据。结论：在近 60% 的原发性散发性脑膜瘤中缺乏完整的 schwannomin/merlin 似乎是脑膜瘤肿瘤发生的一个重要因素。脑膜瘤样脑膜瘤的发展可能与其他癌基因或抑癌基因的改变有关。
OBJECTIVE: The neurofibromatosis type 2 gene is frequently mutated in sporadic meningiomas. The protein product of the neurofibromatosis type 2 gene is called schwannomin or merlin. Its expression in leptomeningeal cells from which meningiomas are derived and the characteristics of mutated forms in meningiomas, to our knowledge, have not been previously studied.METHODS: Immunoblotting and immunoprecipitation experiments with two specific antibodies were used to determine the size and subcellular distribution of schwannomin/merlin in rabbit and human brain tissue and established human leptomeningeal LTAg2B cells. Immunoblotting was used to determine the expression level of schwannomin/merlin in 14 human sporadic meningiomas.RESULTS: Both antibodies detect a protein of approximately 66 kDa, which is predominantly expressed in the Triton X-100-insoluble fraction of the brain and LTAg2B cells. The levels of schwannomin/merlin were severely reduced in eight tumors (57%) when compared with the expression levels in the human brain, LTAg2B cells, and the remaining six meningiomas. All six tumors with the normal schwannomin/merlin expression were of meningo-theliomatous type. In contrast, all other histological types and one meningotheliomatous tumor with psammoma bodies were deficient in the 66-kDa schwannomin/merlin. Although nonsense mutations leading to premature stop codons are common in the neurofibromatosis type 2 gene in meningiomas, we found no evidence of truncated schwannomin/merlin forms in the tumors analyzed.CONCLUSION: The absence of complete schwannomin/merlin in almost 60% of primary sporadic meningiomas seems to be an important factor in meningioma tumorigenesis. The development of meningotheliomatous meningiomas is probably linked to alterations in other oncogenes or tumor suppressor genes.