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ZIC 家族基因在脑膜瘤和其他脑肿瘤中的表达。

Expression of ZIC family genes in meningiomas and other brain tumors.

机构信息

Laboratory for Behavioral and Developmental Disorders, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.

出版信息

BMC Cancer. 2010 Mar 3;10:79. doi: 10.1186/1471-2407-10-79.

DOI:10.1186/1471-2407-10-79
PMID:20199689
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2838823/
Abstract

BACKGROUND

Zic zinc finger proteins are present in the developing rodent meninges and are required for cell proliferation and differentiation of meningeal progenitors. Although human ZIC genes are known to be molecular markers for medulloblastomas, their expression in meningioma has not been addressed to date.

METHODS

We examined the mRNA and protein expression of human ZIC1, ZIC2, ZIC3, ZIC4 and ZIC5 genes in meningiomas in comparison to other brain tumors, using RT-PCR, analysis of published microarray data, and immunostaining.

RESULTS

ZIC1, ZIC2 and ZIC5 transcript levels in meningiomas were higher than those in whole brain or normal dura mater, whereas all five ZIC genes were abundantly expressed in medulloblastomas. The expression level of ZIC1 in public microarray data was greater in meningiomas classified as World Health Organization Grade II (atypical) than those classified as Grade I (benign). Immunoscreening using anti-ZIC antibodies revealed that 23 out of 23 meningioma cases were ZIC1/2/3/5-immunopositive. By comparison, nuclear staining by the anti-ZIC4 antibody was not observed in any meningioma case, but was strongly detected in all four medulloblastomas. ZIC-positive meningiomas included meningothelial, fibrous, transitional, and psammomatous histological subtypes. In normal meninges, ZIC-like immunoreactivities were detected in vimentin-expressing arachnoid cells both in human and mouse.

CONCLUSIONS

ZIC1, ZIC2, and ZIC5 are novel molecular markers for meningiomas whereas ZIC4 expression is highly selective for medulloblastomas. The pattern of ZIC expression in both of these tumor types may reflect the properties of the tissues from which the tumors are derived.

摘要

背景

锌指蛋白 Zic 存在于发育中的啮齿动物脑膜中，对于脑膜祖细胞的增殖和分化是必需的。尽管人类 ZIC 基因被认为是髓母细胞瘤的分子标志物，但它们在脑膜瘤中的表达尚未得到解决。

方法

我们使用 RT-PCR、分析已发表的微阵列数据和免疫染色，比较了脑膜瘤与其他脑肿瘤中人类 ZIC1、ZIC2、ZIC3、ZIC4 和 ZIC5 基因的 mRNA 和蛋白表达。

结果

脑膜瘤中的 ZIC1、ZIC2 和 ZIC5 转录本水平高于整个大脑或正常硬脑膜，而所有五个 ZIC 基因在髓母细胞瘤中均大量表达。公共微阵列数据中 ZIC1 的表达水平在被归类为世界卫生组织 2 级（非典型）的脑膜瘤中高于被归类为 1 级（良性）的脑膜瘤。使用抗 ZIC 抗体进行免疫筛选显示，23 例脑膜瘤中有 23 例为 ZIC1/2/3/5 免疫阳性。相比之下，抗 ZIC4 抗体的核染色在任何脑膜瘤病例中均未观察到，但在所有 4 例髓母细胞瘤中均强烈检测到。ZIC 阳性脑膜瘤包括脑膜上皮型、纤维型、过渡型和砂粒体型组织学亚型。在正常脑膜中，人类和小鼠的蛛网膜细胞中均检测到 vimentin 表达的 ZIC 样免疫反应性。

结论

ZIC1、ZIC2 和 ZIC5 是脑膜瘤的新型分子标志物，而 ZIC4 表达对髓母细胞瘤高度特异。这两种肿瘤类型中 ZIC 的表达模式可能反映了肿瘤来源组织的特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/e361cce48d9b/1471-2407-10-79-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/af0655a485b9/1471-2407-10-79-1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/463b083be324/1471-2407-10-79-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/e0d1a0757171/1471-2407-10-79-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/c4c97a524922/1471-2407-10-79-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/e361cce48d9b/1471-2407-10-79-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/af0655a485b9/1471-2407-10-79-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/7aaca1aaff9b/1471-2407-10-79-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/3c565b2ff878/1471-2407-10-79-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/463b083be324/1471-2407-10-79-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/e0d1a0757171/1471-2407-10-79-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/c4c97a524922/1471-2407-10-79-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5672/2838823/e361cce48d9b/1471-2407-10-79-7.jpg

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