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β-连环蛋白在恶性胶质瘤中的过表达及其在神经胶质母细胞瘤细胞增殖和凋亡中的作用。

β-Catenin overexpression in malignant glioma and its role in proliferation and apoptosis in glioblastma cells.

机构信息

Cerebrovascular Diseases Research Institute, Key Laboratory of Neurodegenerative Diseases of Ministry of Education and Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 100053, Beijing, People's Republic of China.

出版信息

Med Oncol. 2011 Jun;28(2):608-14. doi: 10.1007/s12032-010-9476-5. Epub 2010 Mar 19.

Abstract

β-Catenin, a core component of Wnt/β-catenin signaling, has been shown to be a crucial factor in a broad range of tumors, while its role in glioma is not well understood. In this study, the expression of β-catenin in astrocytic glioma tissues with different grade and human normal cerebral tissues was examined using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. We found a higher expression level of β-catenin in astrocytic glioma patients with high grade in comparison with the normal controls. Additionally, siRNA was transfected into human U251 glioblastoma cells by liposome after the design of siRNA was confirmed to effectively inhibit the expression of β-catenin by RT-PCR. Compared to the control siRNA group, siRNA-mediated knockdown of β-catenin in human U251 cells inhibited cell proliferation, resulted in cell apoptosis, and arrested cell cycle in G₀/G₁. Additionally, downregulation of β-catenin decreased the expression level of cyclin D1, c-Myc and c-jun. Taken together, these results indicate that overexpression of β-catenin may be an important contributing factor to glioma progression.

摘要

β-连环蛋白是 Wnt/β-连环蛋白信号通路的核心组成部分,已被证实是广泛的肿瘤的关键因素,而其在神经胶质瘤中的作用尚不清楚。在这项研究中,采用逆转录-聚合酶链反应(RT-PCR)和免疫组织化学方法检测不同级别星形细胞瘤组织和人正常脑组织中β-连环蛋白的表达。我们发现,与正常对照组相比,高分级星形细胞瘤患者β-连环蛋白的表达水平更高。此外,在设计的 siRNA 被证实能有效地抑制β-连环蛋白的表达后,通过脂质体将 siRNA 转染到人类 U251 神经胶质瘤细胞中。与对照 siRNA 组相比,siRNA 介导的β-连环蛋白下调抑制了人 U251 细胞的增殖,导致细胞凋亡,并使细胞周期停滞在 G₀/G₁期。此外,下调β-连环蛋白降低了细胞周期蛋白 D1、c-Myc 和 c-jun 的表达水平。总之,这些结果表明β-连环蛋白的过度表达可能是神经胶质瘤进展的一个重要因素。

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