Inhibition of transcription factor STAT5b suppresses proliferation, induces G1 cell cycle arrest and reduces tumor cell invasion in human glioblastoma multiforme cells.
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.
Liang
Qin-Chuan
QC
Department of Neurosurgery, Tang-Du Hospital, Institute for Functional Neurosurgery of P.L.A., Fourth Military Medical University, Xin-Si Road, Xi'an 710038, China.
Xiong
Hua
H
Zhao
Zhen-Wei
ZW
Jia
Dong
D
Li
Wei-Xin
WX
Qin
Huai-Zhou
HZ
Deng
Jian-Ping
JP
Gao
Li
L
Zhang
Hua
H
Gao
Guo-Dong
GD
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D016503:Drug Delivery Systems; D016193:G1 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D020033:Protein Isoforms / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors*
D020033:Protein Isoforms; D034741:RNA, Small Interfering; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human