Department of Neurosurgery, Tianjin Medical University General Hospital and Laboratory of Neuro-Oncology, Tianjin Neurological Institute, 152 An-Shan Road, Tianjin, 300052, People's Republic of China.
J Neurooncol. 2010 Jul;98(3):329-40. doi: 10.1007/s11060-009-0092-1. Epub 2009 Dec 25.
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.
我们之前的研究表明,SEPT7 在人胶质瘤中的 mRNA 水平下调。本研究旨在进一步研究 SEPT7 在胶质瘤样本中的表达,并探讨其对细胞周期进程和胶质瘤细胞生长的作用。通过 RT-PCR、免疫组织化学染色和 Western blot 分析检测人胶质瘤标本和正常脑组织中 SEPT7 的 mRNA 和蛋白表达。构建 pcDNA3-SEPT7 表达质粒并转染入人胶质母细胞瘤细胞系 U251,检测细胞增殖和凋亡。在裸鼠中用 pcDNA3-SEPT7 处理建立的 U251 和 TJ905 皮下移植性脑肿瘤,并处理 SEPT7 siRNA 转染的 U251 移植瘤,测量其生长情况。SEPT7 的表达与胶质瘤分级的增加呈负相关。过表达 SEPT7 能够在体外和体内抑制细胞增殖并阻滞细胞周期在 G0/G1 期。用 siRNA 进一步敲低 U251 移植瘤中已经较低的内源性 SEPT7 表达,与对照肿瘤相比,导致肿瘤生长更快。本研究表明 SEPT7 参与胶质瘤的发生,并抑制胶质瘤细胞的生长。