McCutcheon Ian E, Hentschel Stephen J, Fuller Gregory N, Jin Wei, Cote Gilbert J
Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Neuro Oncol. 2004 Jan;6(1):9-14. doi: 10.1215/S1152851703000279.
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 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 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 (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.
多聚嘧啶序列结合蛋白（PTB）是一种核因子，它与前体mRNA内含子的多聚嘧啶序列结合，在那里它与RNA剪接的负调控以及外显子沉默相关。我们之前已经证明，PTB的表达在胶质细胞转化过程中增加，并且这种增加与脑以及胶质和神经元肿瘤中的变化相关。石蜡切片用抗PTB的一抗进行染色。分析的组织包括正常组织和成纤维细胞生长因子受体1的RNA剪接发生变化的组织。在本文中，我们研究了PTB表达在正常脑（n = 2）和各种类型肿瘤（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；发育异常性神经节细胞瘤，n = 1；神经节胶质瘤，n = 1；副神经节瘤，n = 1）中的特定细胞分布。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，但偶尔可观察到阳性染色细胞。在室管膜细胞、脉络丛上皮、小胶质细胞、蛛网膜和腺垂体中观察到PTB强阳性染色，在神经垂体中发现弱阳性染色。在所有情况下，血管内皮和平滑肌染色均为强阳性。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、副神经节瘤以及神经节胶质瘤和发育异常性神经节细胞瘤的胶质细胞群体的转化细胞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，其他细胞谱系也是如此。在正常脑中，所有神经元群体和松果体细胞的PTB均为阴性。我们得出结论，尽管胶质细胞显示PTB表达去抑制，但在非肿瘤性神经元和大多数神经元来源的肿瘤细胞中不存在类似机制。胶质或原始神经外胚层来源的肿瘤细胞中PTB表达的强烈上调表明该蛋白参与细胞转化。PTB是否影响对细胞转化或增殖至关重要的RNA剪接是未来研究的一个重要问题。
