Constitutive activation of signal transducer and activator of transcription 3 regulates expression of vascular endothelial growth factor in human meningioma differentiation.
OBJECTIVE
Janus tyrosine kinases (JAKs) and signal transducer and activator of transcription factors (STATs), especially STAT3, are constitutively activated in human cancers. The function of STAT3 in the pathogenesis of meningioma remains unknown. In this study, we investigated the role of JAK1/STAT3 regulating vascular endothelial growth factor (VEGF) expression in the occurrence and progression of human meningioma.


METHODS
We detected the expression of JAK1, p-JAK1, STAT3, p-STAT3, and VEGF in human meningioma and normal dura tissues by RT-PCR, Western blot analysis, and immunohistochemistry.


RESULTS
JAK1, p-JAK1, STAT3, p-STAT3, and VEGF showed high expression in grade I and grade II meningioma. The level of STAT3 activation was associated with VEGF expression; all meningioma tumors that expressed p-STAT3 also expressed VEGF. Both frequency of positivity and expression were enhanced with increasing tumor grade; high frequencies and levels were found in grade II tumors, with no expression detected in normal dura tissues (P < 0.05).


CONCLUSIONS
VEGF is directly regulated by constitutive STAT3 activity and associated with meningioma differentiation. STAT3 has an important role in the occurrence and development of human meningioma by regulating VEGF expression.
Zhang
Mao Xiu
MX
Department of Microbiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, 250012 Jinan, Shandong, People's Republic of China.
Zhao
Xu
X
Wang
Zhi Gang
ZG
Zhao
Wei Ming
WM
Wang
Yun Shan
YS
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D042461:Vascular Endothelial Growth Factor A; C507904:JAK1 protein, human; D053613:Janus Kinase 1