Institute of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
Histol Histopathol. 2011 Dec;26(12):1531-43. doi: 10.14670/HH-26.1531.
Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumour. Protein tyrosine phosphatase interacting protein 51 (PTPIP51) is an interaction partner of 14-3-3β, which correlates with the grade of malignancy in gliomas. In this study PTPIP51 and its interacting partners 14-3-3β, PTP1B, c-Src, Raf-1 as well as EGFR were investigated in human glioblastoma. Twenty glioblastoma samples were analyzed on transcriptional and translational level by immunohistochemistry, in situ hybridization and RT-PCR. To compare PTPIP51 expression in gliomas of different malignancies, quantitative RT-PCR for grade II astrocytoma and GBM samples was employed. Additionally, we analyzed the correlation between PTPIP51 and 14-3-3β transcription, and checked for in situ interaction between PTPIP51 and 14-3-3β and PTP1B, respectively. PTPIP51 and 14-3-3β mRNA showed a tumour grade dependent upregulation in gliomas. Glioblastoma cells displayed a strong immunoreaction of PTPIP51, which co-localized with 14-3-3β and PTP1B. The duolink proximity ligation assay corroborated a direct in situ interaction of PTPIP51 with both proteins, known to interact with PTPIP51 in vitro. The in vitro interacting partners Raf-1 and c-Src showed a partial co-localization. Besides, immune cells located in capillaries or infiltrating the tumour tissue and endothelial cells of pseudoglomerular vessels revealed a high PTPIP51 expression. The upregulation of PTPIP51 and its connection with the EGFR/MAPK pathway by 14-3-3β via Raf-1 and by PTP1B via c-Src, argue for a functional role of PTPIP51 in the pathogenesis of human glioblastoma.
多形性胶质母细胞瘤（GBM）是最常见和最恶性的原发性脑肿瘤。蛋白酪氨酸磷酸酶相互作用蛋白 51（PTPIP51）是 14-3-3β 的相互作用伙伴，与神经胶质瘤的恶性程度相关。在这项研究中，研究人员在人类胶质母细胞瘤中研究了 PTPIP51 及其相互作用伙伴 14-3-3β、PTP1B、c-Src、Raf-1 和 EGFR。通过免疫组织化学、原位杂交和 RT-PCR 分析了 20 例胶质母细胞瘤样本的转录和翻译水平。为了比较不同恶性程度的神经胶质瘤中 PTPIP51 的表达，采用定量 RT-PCR 分析了 II 级星形细胞瘤和 GBM 样本。此外，还分析了 PTPIP51 和 14-3-3β 转录之间的相关性，并分别检查了 PTPIP51 与 14-3-3β 和 PTP1B 之间的原位相互作用。PTPIP51 和 14-3-3β mRNA 在神经胶质瘤中表现出肿瘤分级依赖性上调。胶质母细胞瘤细胞显示出强烈的 PTPIP51 免疫反应，与 14-3-3β 和 PTP1B 共定位。duolink 邻近连接分析证实了 PTPIP51 与这两种蛋白质的直接原位相互作用，这两种蛋白质在体外与 PTPIP51 相互作用。体外相互作用伙伴 Raf-1 和 c-Src 显示出部分共定位。此外，位于毛细血管内或浸润肿瘤组织的免疫细胞和假肾小球血管的内皮细胞显示出高 PTPIP51 表达。PTPIP51 的上调及其与 EGFR/MAPK 通路的连接通过 14-3-3β 通过 Raf-1 以及通过 PTP1B 通过 c-Src，表明 PTPIP51 在人类胶质母细胞瘤的发病机制中具有功能作用。
