Activating transcription factor 3 is overexpressed in human glioma and its knockdown in glioblastoma cells causes growth inhibition both in vitro and in vivo.
Activating transcription factor 3 is overexpressed in human glioma and its knockdown in glioblastoma cells causes growth inhibition both in vitro and in vivo.
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DOI：
10.3892/ijmm.2015.2173
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发表时间：
2015-06
影响因子：
5.4
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Ma S;Pang C;Song L;Guo F;Sun H
胶质母细胞瘤是高度恶性的胶质瘤，具有极强的侵袭性，复发率和死亡率高。有报道称，激活转录因子3 （ATF3）在多种恶性肿瘤中表达水平升高。本研究旨在探讨ATF3在胶质瘤发生发展中的作用及其临床意义。免疫组化染色、western blot和RT-qPCR结果显示，脑胶质瘤组织中ATF3和基质金属蛋白酶2 (matrix metalloproteinase 2, MMP2) mRNA和蛋白水平均高于正常人脑组织，且与病理分级成正比。而乳腺丝氨酸蛋白酶抑制剂（maspin; SERPINB5） mRNA和蛋白水平在胶质瘤中明显低于正常脑组织，且maspin的表达与胶质瘤病理分级成反比。用ATF3-siRNA转染U373MG胶质母细胞瘤细胞可引起细胞行为的一系列变化；细胞增殖活性下降，流式细胞术显示在细胞周期的G0/G1期停滞的细胞比例增加。此外，TUNEL染色显示细胞凋亡比例增加，Transwell实验显示细胞流动性受损。用ATF3-siRNA处理宿主小鼠后，在裸鼠体内生长的异种移植物肿瘤的大小也显著减小。综上所述，这些结果表明ATF3促进了人类胶质瘤的进展。
Glioblastomas are highly malignant gliomas that are extremely invasive with high rates of recurrence and mortality. It has been reported that activating transcription factor 3 (ATF3) is expressed in elevated levels in multiple malignant tumors. The purpose of this study was to investigate the function of ATF3 in the development of glioma and its clinical significance. Immunohistochemical staining, western blot analysis and RT-qPCR revealed that the mRNA and protein levels of ATF3 and matrix metalloproteinase 2 (MMP2) were higher in the glioma than in the normal human brain tissues, and that their levels were proportional to the pathological grades. By contrast, the mRNA and protein levels of mammary serine protease inhibitor (maspin; SERPINB5) were significantly lower in the glioma than in the normal brain tissue, and maspin expression was inversely proportional to the glioma pathological grade. The transfection of U373MG glioblastoma cells with ATF3-siRNA induced a number of changes in cell behavior; the cell proliferative activity was decreased and flow cytometry revealed an increased proportion of cells arrested in the G0/G1 phase of the cell cycle. In addition, TUNEL staining indicated an increased proportion of cells undergoing apoptosis and Transwell assays revealed impaired cell mobility. The sizes of the tumors grown as xenografts in nude mice were also significantly reduced by treatment of host mice with ATF3-siRNA. Taken together, these results suggest that ATF3 promotes the progression of human gliomas.
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影响因子：
4.8
作者：
Ngamkitidechakul, C;Warejcka, DJ;Twining, SS
通讯作者：
Twining, SS
DOI：
10.1073/pnas.88.9.3720
发表时间：
1991-05-01
影响因子：
11.1
作者：
HAI, T;CURRAN, T
通讯作者：
CURRAN, T
DOI：
10.1073/pnas.97.8.3884
发表时间：
2000-04-11
影响因子：
11.1
作者：
Fang, JM;Shing, Y;Moses, MA
通讯作者：
Moses, MA
影响因子：
11.2
作者：
Song H;Li Y;Lee J;Schwartz AL;Bu G
通讯作者：
Bu G
影响因子：
25.7
作者：
Musso, O;Theret, N;Clement, B
通讯作者：
Clement, B