Overexpression of septin 7 suppresses glioma cell growth

Overexpression of septin 7 suppresses glioma cell growth
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septin 7 的过度表达抑制神经胶质瘤细胞生长

DOI:
10.1007/s11060-009-0092-1
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发表时间:
2010-07-01
影响因子:
3.9
通讯作者:
Pu, Pei-yu
Pu, Pei-yu
中科院分区:
医学2区
文献类型:
--
作者:
Jia, Zhi-fan;Huang, Qiang;Pu, Pei-yu

文献摘要

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我们前期的研究表明SEPT 7在人脑胶质瘤中mRNA水平下调。本研究旨在进一步检测SEPT 7在胶质瘤样本中的表达,并表征其对胶质瘤细胞细胞周期进程和生长的作用。采用RT-PCR、免疫组化和western blot方法检测SEPT 7在人脑胶质瘤和正常脑组织中的mRNA和蛋白表达。构建真核表达质粒pcDNA 3-SEPT 7,转染人胶质母细胞瘤细胞系U251,观察细胞增殖和凋亡情况。在用pcDNA 3-SEPT 7处理的裸鼠和用SEPT 7 siRNA处理的U251异种移植肿瘤中测量建立的U251和TJ 905皮下异种移植胶质瘤的生长。SEPT 7的表达与胶质瘤的分级呈负相关。SEPT 7的过表达能够在体外和体内抑制细胞增殖并将细胞周期进程阻滞在G 0/G1期。与对照肿瘤相比,用siRNA进一步敲低U251异种移植肿瘤中已经低的SEPT 7内源性表达导致更快的肿瘤生长。这项研究表明,SEPT 7参与胶质瘤的发生,并抑制胶质瘤细胞的生长。
Our previous study demonstrated that SEPT7 was downregulated at mRNA level in human gliomas. This study is to further examine the expression of SEPT7 in glioma samples and characterizes its role on cell cycle progression and growth of glioma cells. mRNA and protein expression of SEPT7 were detected by RT-PCR, immunohistochemical staining, and western blot analysis in human glioma specimens and normal brain tissues. A pcDNA3-SEPT7 expression plasmid was constructed and transfected into human glioblastoma cell line U251, and cell proliferation and apoptosis were examined. The growth of established U251 and TJ905 subcutaneous xenograft gliomas was measured in nude mice treated with pcDNA3-SEPT7 and U251 xenograft tumors treated with SEPT7 siRNA. SEPT7 expression is negatively correlated with the increase of glioma grade. Overexpression of SEPT7 is able to inhibit cell proliferation and arrest cell cycle progression in the G0/G1 phase both in vitro and in vivo. Knocking down further the already low endogenous expression of SEPT7 in U251 xenograft tumors with siRNA leads to faster tumor growth compared with control tumors. This study demonstrates that SEPT7 is involved in gliomagenesis and suppresses glioma cell growth.