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信号转导子和转录激活子 3 的组成性激活调节人脑膜瘤分化中血管内皮生长因子的表达。

Constitutive activation of signal transducer and activator of transcription 3 regulates expression of vascular endothelial growth factor in human meningioma differentiation.

机构信息

Department of Microbiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, 250012 Jinan, Shandong, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2010 Jul;136(7):981-8. doi: 10.1007/s00432-009-0743-9. Epub 2010 Jan 6.

Abstract

PURPOSE

Janus tyrosine kinases (JAKs) and signal transducer and activator of transcription factors (STATs), especially STAT3, are constitutively activated in human cancers. The function of STAT3 in the pathogenesis of meningioma remains unknown. In this study, we investigated the role of JAK1/STAT3 regulating vascular endothelial growth factor (VEGF) expression in the occurrence and progression of human meningioma.

METHODS

We detected the expression of JAK1, p-JAK1, STAT3, p-STAT3, and VEGF in human meningioma and normal dura tissues by RT-PCR, Western blot analysis, and immunohistochemistry.

RESULTS

JAK1, p-JAK1, STAT3, p-STAT3, and VEGF showed high expression in grade I and grade II meningioma. The level of STAT3 activation was associated with VEGF expression; all meningioma tumors that expressed p-STAT3 also expressed VEGF. Both frequency of positivity and expression were enhanced with increasing tumor grade; high frequencies and levels were found in grade II tumors, with no expression detected in normal dura tissues (P < 0.05).

CONCLUSIONS

VEGF is directly regulated by constitutive STAT3 activity and associated with meningioma differentiation. STAT3 has an important role in the occurrence and development of human meningioma by regulating VEGF expression.

摘要

目的

Janus 酪氨酸激酶(JAKs)和信号转导子和转录激活因子(STATs),特别是 STAT3,在人类癌症中持续激活。STAT3 在脑膜瘤发病机制中的作用尚不清楚。在这项研究中,我们研究了 JAK1/STAT3 调节血管内皮生长因子(VEGF)表达在人脑膜瘤发生和进展中的作用。

方法

我们通过 RT-PCR、Western blot 分析和免疫组织化学检测了人脑膜瘤和正常硬脑膜组织中 JAK1、p-JAK1、STAT3、p-STAT3 和 VEGF 的表达。

结果

JAK1、p-JAK1、STAT3、p-STAT3 和 VEGF 在 I 级和 II 级脑膜瘤中高表达。STAT3 的激活水平与 VEGF 的表达相关;所有表达 p-STAT3 的脑膜瘤肿瘤均表达 VEGF。随着肿瘤分级的增加,阳性率和表达水平均增强;在 II 级肿瘤中阳性率和水平较高,在正常硬脑膜组织中未检测到表达(P<0.05)。

结论

VEGF 受组成性 STAT3 活性的直接调节,并与脑膜瘤分化相关。STAT3 通过调节 VEGF 表达在人脑膜瘤的发生和发展中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57dc/11827908/6ea9f0293fd8/432_2009_743_Fig1_HTML.jpg

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