Nerve Growth Factor Stimulates Glioblastoma Proliferation through Notch1 Receptor Signaling.
Nerve Growth Factor Stimulates Glioblastoma Proliferation through Notch1 Receptor Signaling.
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DOI：
10.3340/jkns.2017.0219
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发表时间：
2018-07
影响因子：
1.6
通讯作者：
Park YH
中科院分区：
文献类型：
--
作者：
Park JC;Chang IB;Ahn JH;Kim JH;Song JH;Moon SM;Park YH
Notch受体是一种异源二聚体跨膜蛋白，调节细胞的命运，如分化、增殖和凋亡。在胶质母细胞瘤以及其他人类恶性肿瘤中也观察到了Notch通路信号的失调。神经生长因子(NGF)是神经系统细胞生长和分化所必需的。最近的报道表明，NGF刺激了胶质母细胞瘤的增殖。然而，神经生长因子和Notch1在胶质母细胞瘤中的关系尚不清楚。因此，我们研究了Notch1在胶质母细胞瘤细胞系(U87-MG)中的表达，并探讨了NGF与Notch1信号转导的关系。我们用免疫组织化学方法检测了Notch1在人脑胶质母细胞瘤和正常脑组织中的表达。用4-(4，5-二甲基噻唑-2-基)-2，5-二苯基四氮唑(MTT)比色法检测NGF对胶质母细胞瘤细胞株(U87-MG)的作用。为探讨NGF与Notch1信号转导的关系，分别采用逆转录聚合酶链式反应(RT-PCR)和Western印迹分析Notch1和Hes1的表达。为了证实NGF对Notch1信号转导的影响，使用Notch1和Hes1小干扰RNA(SiRNAs)。免疫组织化学显示，Notch1在胶质母细胞瘤中的表达高于正常脑组织。四甲基偶氮唑盐比色法显示NGF对U87-MG细胞的刺激作用呈剂量依赖关系。RT-PCR和Western印迹分析表明，NGF可剂量依赖性地上调Notch1和Hes1的表达。转染Notch1和Hes1 siRNAs后，对照组和100 nM NGF-β细胞的增殖无明显差异，说明Notch1和Hes1 siRNAs抑制了U87-MG细胞的增殖。这些结果表明，NGF通过Hes1途径通过Notch1信号途径刺激胶质母细胞瘤细胞增殖。
Notch receptors are heterodimeric transmembrane proteins that regulate cell fate, such as differentiation, proliferation, and apoptosis. Dysregulated Notch pathway signaling has been observed in glioblastomas, as well as in other human malignancies. Nerve growth factor (NGF) is essential for cell growth and differentiation in the nervous system. Recent reports suggest that NGF stimulates glioblastoma proliferation. However, the relationship between NGF and Notch1 in glioblastomas remains unknown. Therefore, we investigated expression of Notch1 in a glioblastoma cell line (U87-MG), and examined the relationship between NGF and Notch1 signaling. We evaluated expression of Notch1 in human glioblastomas and normal brain tissues by immunohistochemical staining. The effect of NGF on glioblastoma cell line (U87-MG) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. To evaluate the relationship between NGF and Notch1 signaling, Notch1 and Hes1 expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To confirm the effects of NGF on Notch1 signaling, Notch1 and Hes1 small interfering RNAs (siRNAs) were used. In immunohistochemistry, Notch1 expression was higher in glioblastoma than in normal brain tissue. MTT assay showed that NGF stimulates U87-MG cells in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated that Notch1 and Hes1 expression were increased by NGF in a dose-dependent manner. After transfection with Notch1 and Hes1 siRNAs, there was no significant difference between controls and 100 nM NGF-β, which means that U87-MG cell proliferation was suppressed by Notch1 and Hes1 siRNAs. These results indicate that NGF stimulates glioblastoma cell proliferation via Notch1 signaling through Hes 1.
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影响因子：
3
作者：
Qian XQ;Chen LL;Cheng Q;Tian Y;Luo XF;Wan XY
通讯作者：
Wan XY
影响因子：
7.5
作者：
Cheung, Hannah C.;Corley, Lynda J.;Cote, Gilbert J.
通讯作者：
Cote, Gilbert J.
影响因子：
3.2
作者：
Aster, JC;Pear, WS
通讯作者：
Pear, WS
影响因子：
5.3
作者：
Bigas, A;Martin, DIK;Milner, LA
通讯作者：
Milner, LA
影响因子：
5.2
作者：
Giraud, Stephanie;Loum, Elodie;Lalloue, Fabrice
通讯作者：
Lalloue, Fabrice