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神经节细胞瘤中丝裂原活化蛋白激酶的上调。

Upregulation of mitogen-activated protein kinase in ganglioglioma.

机构信息

Jarosław Jóźwiak, Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, ul. Chalubinskiego 5, 02-004 Warsaw, Poland, fax: +48 22 629 52 82, e-mail:

出版信息

Folia Neuropathol. 2013;51(4):283-9. doi: 10.5114/fn.2013.39717.

Abstract

Ganglioglioma (GG) is a low-grade neoplasm, often associated with intractable epilepsy in pediatric patients. Available data suggest a relationship between GG and other glioneuronal lesions. So far, little is known about activation of kinases belonging to the mTor (mammalian target of rapamycin) pathway, although its upregulation is often found in brain tumors. Involvement of mTor kinase is responsible for excessive proliferation. In the current study we focused on the possible role of the Erk/Mapk (extracellular-signal-regulated kinase/mitogen-activated protein kinase) pathway in GG development. Eight GG tumors were resected from pediatric patients. Collected data reveal activation of proteins from the Erk pathway: Mek (extracellular regulated protein kinase kinase/mitogen-activated protein kinase kinase), Erk, Rsk1 (ribosomal S6 kinase 1), Rheb (Ras homolog enriched in brain) and Msk1 (mitogen- and stress-activated protein kinase 1), as detected by the western blot method. Moreover, activation of other proteins upstream of mTor - IGF-1R β (insulin-like growth factor 1β receptor), INR β (insulin receptor β), Akt/PKB (protein kinase B) - or downstream - 4E-BP1 (eukaryotic translation initiation factor 4E-binding protein 1) and rpS6 (ribosomal protein S6) - was also confirmed.

摘要

神经节神经胶质瘤(GG)是一种低级别的肿瘤,常与儿科患者的难治性癫痫有关。现有数据表明 GG 与其他神经胶质病变之间存在关联。到目前为止,人们对属于 mTor(哺乳动物雷帕霉素靶蛋白)途径的激酶的激活知之甚少,尽管其在脑肿瘤中经常上调。mTor 激酶的参与负责过度增殖。在本研究中,我们专注于 Erk/Mapk(细胞外信号调节激酶/有丝分裂原激活蛋白激酶)途径在 GG 发展中的可能作用。从儿科患者中切除了 8 个 GG 肿瘤。收集的数据显示 Erk 通路蛋白的激活:Mek(细胞外调节蛋白激酶激酶/有丝分裂原激活蛋白激酶激酶)、Erk、Rsk1(核糖体 S6 激酶 1)、Rheb(富含大脑的 Ras 同源物)和 Msk1(有丝分裂和应激激活蛋白激酶 1),通过 western blot 方法检测到。此外,还证实了 mTor 上游的其他蛋白质的激活-IGF-1Rβ(胰岛素样生长因子 1β受体)、INRβ(胰岛素受体β)、Akt/PKB(蛋白激酶 B)-或下游-4E-BP1(真核翻译起始因子 4E 结合蛋白 1)和 rpS6(核糖体蛋白 S6)。

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