Polypyrimidine tract binding protein and Notch1 are independently re-expressed in glioma
Polypyrimidine tract binding protein and Notch1 are independently re-expressed in glioma
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DOI：
10.1038/modpathol.3800635
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发表时间：
2006-08-01
期刊：
影响因子：
7.5
通讯作者：
Cote, Gilbert J.
中科院分区：
文献类型：
--
作者：
Cheung, Hannah C.;Corley, Lynda J.;Cote, Gilbert J.
多聚嘧啶束结合蛋白（PTB）在发育中的哺乳动物星形胶质细胞中表达，在成熟的成体星形胶质细胞中缺失，在胶质瘤中异常升高。目前还不清楚PTB是否是肿瘤进展的巧合标志物或肿瘤发生的重要介质。在发育中的果蝇中，PTB同源物hephaestus的缺失导致Notch活性增加。由于Notch是一种众所周知的神经胶质细胞命运诱导剂，我们确定了PTB在神经胶质细胞肿瘤中的过表达是否通过抑制活化的Notch（Notch1IC）介导的分化提供了选择性生长优势。为了做到这一点，我们进行了一个广泛的人类组织微阵列，包括246个胶质瘤，10个胶质瘤，和10个正常的大脑PTB，激活Notch1（Notch1IC），Hes1（Notch目标）和GFAP的表达免疫组化分析。在所有级别的胶质瘤中均观察到统计学显着的PTB过表达，其中IV级肿瘤的增幅最高。Notch1IC在胶质瘤中也异常表达，除了在IV级肿瘤的子集中不存在。Notch1IC的这种减少与PTB表达的增加无关。我们的结论是PTB和Notch1作为胶质瘤进展的独立和功能无关的标志物。
Polypyrimidine tract binding protein (PTB) is expressed in developing mammalian astrocytes, absent in mature adult astrocytes, and aberrantly elevated in gliomas. It is unclear whether PTB is a coincidental marker of tumor progression or a significant mediator of tumorigenesis. In developing Drosophila, the absence of the PTB homolog, hephaestus, results in increased Notch activity. Since Notch is a well-known inducer of glial cell fate, we determined whether overexpression of PTB in glial cell tumors provides a selective growth advantage by inhibiting activated Notch (Notch1IC)-mediated differentiation. To do this, we performed an immunohistochemical analysis for expression of PTB, activated Notch1 (Notch1IC), Hes1 (a Notch target), and GFAP on an extensive human tissue microarray that included 246 gliomas, 10 gliosarcomas, and 10 normal brains. Statistically significant PTB overexpression was seen in all glioma grades, with the highest increase in grade IV tumors. Notch1IC was also abnormally expressed in gliomas except in a subset of grade IV tumors in which it was absent. This decrease in Notch1IC was not associated with increased PTB expression. We conclude that PTB, and Notch1 serve as independent and functionally unlinked markers of glioma progression.