Expression of the splicing regulator polypyrimidine tract-binding protein in normal and neoplastic brain
Expression of the splicing regulator polypyrimidine tract-binding protein in normal and neoplastic brain
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DOI：
10.1215/s1152851703000279
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发表时间：
2004-01-01
期刊：
影响因子：
15.9
通讯作者：
Cote, GJ
中科院分区：
文献类型：
--
作者：
McCutcheon, IE;Hentschel, SJ;Cote, GJ
多聚嘧啶片段结合蛋白（PTB）是一种核因子，与前体mRNA内含子的多聚嘧啶片段结合，与RNA剪接的负调控和外显子沉默相关。我们以前已经证明，PTB的表达增加，在神经胶质细胞转化，这种增加与成纤维细胞生长因子受体1的RNA剪接的变化。在本文中，我们研究了特定的细胞分布的PTB表达在正常脑和神经胶质细胞和神经元肿瘤。通过使用抗PTB的一级单克隆抗体对石蜡切片进行染色。分析的组织包括正常脑（n = 2）和各种类型的肿瘤（低级别星形细胞瘤，n = 2;间变性星形细胞瘤，n = 2;胶质母细胞瘤，n = 4;髓母细胞瘤，n = 4;中枢神经细胞瘤，n = 2;发育不良神经节细胞瘤，n = 1;神经节胶质瘤，n = 1;副神经节瘤，n = 1）。在胶质细胞群体中，大多数星形胶质细胞和少突胶质细胞为阴性，但偶尔观察到阳性染色细胞。PTB强阳性染色见于室管膜细胞、脉络丛上皮、小胶质细胞、蛛网膜和腺垂体，弱阳性染色见于神经垂体。在所有情况下，血管内皮和平滑肌染色强烈。在肿瘤样本中，在低级别星形细胞瘤、间变性星形细胞瘤、多形性胶质母细胞瘤、髓母细胞瘤、副神经节瘤的转化细胞以及神经节细胞胶质瘤和发育不良性神经节细胞瘤的胶质细胞群中观察到强烈的阳性核染色（两者的神经元细胞均为阴性）。在髓母细胞瘤中，肿瘤性神经元细胞呈阳性，其他细胞系也呈阳性。在正常脑中，所有神经元群体和松果体细胞均为PTB阴性。我们的结论是，尽管胶质细胞表现出PTB表达的去抑制，但在非肿瘤神经元和大多数神经源性肿瘤细胞中都不存在类似的机制。PTB在神经胶质或原始神经外胚层肿瘤细胞中的表达强烈上调。起源表明这种蛋白质参与细胞转化。PTB是否影响RNA的剪接对细胞转化或增殖至关重要，是未来研究的一个重要问题。
Polypyrimidine tract-binding protein (PTB) is a nuclear factor that binds to the polypyrimidine tract of pre-mRNA introns, where it is associated with negative regulation of RNA splicing and with exon silencing. We have previously demonstrated that PTB expression is increased during glial cell transformation and that this increase correlates with changes in the RNA splicing of the fibroblast growth factor receptor 1. In this paper we examine the specific cellular distribution of PTB expression in normal brain and in glial and neuronal tumors. Paraffin sections were stained by using a primary monoclonal antibody against PTB. Tissues that were analyzed included normal brain (n = 2) and tumors of various types (low-grade astrocytoma, n = 2; anaplastic astrocytoma, n = 2; glioblastoma, n = 4; medulloblastoma, n = 4; central neurocytoma, n = 2; dysplastic gangliocytoma, n = 1; ganglioglioma, n = 1; paraganglioma, n = 1). In glial cell populations the majority of astrocytes and oligodendrocytes were negative, but occasional positively staining cells were observed. Strongly positive PTB staining was observed in ependymocytes, choroid plexus epithelium, microglia, arachnoid membrane, and adenohypophysis, and weak staining was found in the neurohypophysis. In all cases vascular endothelium and smooth muscle stained strongly. In tumor samples, intense positive nuclear staining was observed in transformed cells of low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, medulloblastoma, paraganglioma, and the glial population of both ganglioglioma and dysplastic gangliocytoma (the neuronal cells of both were negative). In medulloblastoma, neoplastic neuronal cells were positive, as were other cell lineages. In normal brain, all neuron populations and pineocytes were negative for PTB. We conclude that although glial cells show derepression of PTB expression, a similar mechanism is absent in both nonneoplastic neurons and in most neuronally derived tumor cells. Strong upregulation of PTB expression in tumor cells of glial or primitive neuroectodermal. origin suggests involvement of this protein in cellular transformation. Whether PTB affects splicing of RNAs critical to cellular transformation or proliferation is an important question for future research.