Inhibition of transcription factor STAT5b suppresses proliferation, induces G1 cell cycle arrest and reduces tumor cell invasion in human glioblastoma multiforme cells

被引:72
作者
Liang, Qin-Chuan [1 ]
Xiong, Hua [2 ]
Zhao, Zhen-Wei [1 ]
Jia, Dong [1 ]
Li, Wei-Xin [1 ]
Qin, Huai-Zhou [1 ]
Deng, Jian-Ping [1 ]
Gao, Li [1 ]
Zhang, Hua [1 ]
Gao, Guo-Dong [1 ]
机构
[1] Fourth Mil Med Univ, Inst Funct Neurosurg PLA, Tang Du Hosp, Dept Neurosurg, Xian 710038, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Dept Gastroenterol, Ren Ji Hosp,Shanghai Inst Digest Dis, Shanghai 200001, Peoples R China
关键词
Glioblastoma multiforme; STAT5 signaling pathway; STAT5; isoforms; CARCINOGENESIS IN-VIVO; CONSTITUTIVE ACTIVATION; SIGNAL TRANSDUCER; MALIGNANT GLIOMA; GENE-EXPRESSION; PROSTATE-CANCER; BRAIN-TUMORS; APOPTOSIS; LOCALIZATION; FIBROBLASTS;
D O I
10.1016/j.canlet.2008.08.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Abnormalities in the signal transducer and activator of transcription 5 (STAT5) signaling are involved in the oncogenesis of several cancers. However, previous studies have not elucidated clear and distinct roles for each STAT5 gene in cancers. To investigate the role of STAT5a, -5b isoforms in human glioblastoma multiforme (GBM) progression, we depleted each STAT5 isoforms with siRNA. Our results demonstrate that STAT5b is involved in GBM cell growth, cell cycle progression, invasion and migration through regulation of gene expression, such as Bcl-2, p21(waf1/cip1), p27(kip1), FAK and VEGF. Moreover, immunohistochemical staining reveals that cytoplasm staining of STAT5b is markedly increased in GBM (57.1%) compared with that in normal cortex (22.2%) and diffuse astrocytoma (27.3%), suggesting that STAT5b could have important implications in astrocytoma biology. Therefore, our findings illustrate the biological significance of STAT5b in GBM progression, and provide novel evidence that STAT5b may serve as a therapeutic target in the prevention of human glioblastoma multiforme. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:164 / 171
页数:8
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