Harwalkar J A, Lee J H, Hughes G, Kinney S E, Golubić M
Department of Neurosurgery, Cleveland Clinic Foundation, Ohio 44195, USA.
Am J Otol. 1998 Sep;19(5):654-9.
Absent or reduced expression of schwannomin/merlin is associated with tumorigenesis of sporadic schwannomas.
The neurofibromatosis type 2 (NF2) gene frequently is mutated in sporadic vestibular schwannomas. The protein product of the NF2 gene is called schwannomin or merlin. Little is known about the mutated forms of schwannomin/merlin present in schwannomas.
To investigate further the role of schwannomin/merlin in schwannoma tumorigenesis, immunoblotting experiments were performed. Antischwannomin/merlin-specific antibody that recognizes amino terminus of the protein was used to determine the expression levels of schwannomin/merlin in 16 sporadic vestibular schwannomas, 1 NF2-related vestibular schwannoma, and 5 spinal schwannomas.
The antibody detects a protein of approximately 66 kDa in the Triton X-100-insoluble fraction of tumors. The expression of schwannomin/merlin was severely reduced, <35% of control, in 11 (50%) of 22 sporadic schwannomas and in 1 NF2-related vestibular schwannoma. The intensity of 66-kDa schwannomin/merlin band was moderately reduced, from 35-60%, in 7 (32%) of 22 schwannomas compared to the expression levels found in the human brain. Truncated forms of schwannomin/merlin were identified in three tumors with moderately reduced schwannomin/merlin.
These results provide new evidence that inactivation of schwannomin/merlin is an important factor in tumorigenesis of sporadic schwannomas.
施万蛋白/默林蛋白表达缺失或降低与散发性神经鞘瘤的发生有关。
2型神经纤维瘤病（NF2）基因在散发性前庭神经鞘瘤中经常发生突变。NF2基因的蛋白质产物称为施万蛋白或默林蛋白。人们对神经鞘瘤中存在的施万蛋白/默林蛋白的突变形式知之甚少。
为了进一步研究施万蛋白/默林蛋白在神经鞘瘤发生中的作用，进行了免疫印迹实验。使用识别该蛋白氨基末端的抗施万蛋白/默林蛋白特异性抗体，来测定16例散发性前庭神经鞘瘤、1例NF2相关前庭神经鞘瘤和5例脊髓神经鞘瘤中施万蛋白/默林蛋白的表达水平。
该抗体在肿瘤的Triton X - 100不溶性部分检测到一种约66 kDa的蛋白质。在22例散发性神经鞘瘤中的11例（50%）以及1例NF2相关前庭神经鞘瘤中，施万蛋白/默林蛋白的表达严重降低，低于对照的35%。与人类大脑中的表达水平相比，22例神经鞘瘤中的7例（32%）中66 kDa施万蛋白/默林蛋白条带的强度中度降低，为35% - 60%。在3例施万蛋白/默林蛋白中度降低的肿瘤中鉴定出了截短形式的施万蛋白/默林蛋白。
这些结果提供了新的证据，表明施万蛋白/默林蛋白的失活是散发性神经鞘瘤发生的一个重要因素。
