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Constitutive activation of signal transducer and activator of transcription 3 regulates expression of vascular endothelial growth factor in human meningioma differentiation.

Zhang MX, Zhao X, Wang ZG, Zhao WM, Wang YS - J. Cancer Res. Clin. Oncol. (2010)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, 250012 Jinan, Shandong, People's Republic of China.

ABSTRACT

Purpose: 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.

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Related in: MedlinePlus

Plots of gene expression from RT-PCR and Western blot analysis in normal dura and meningioma tissues normalized to that of Beta-actin. Relative mRNA expression of JAK1, STAT3, and VEGFa in a normal dura tissue, b grade I tissue, and c grade II tissue. Relative protein expression of JAK1, p-JAK1, STAT3, p-STAT3, and VEGF in d normal dura tissue, e grade I tissue, and f grade II tissue
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Fig2: Plots of gene expression from RT-PCR and Western blot analysis in normal dura and meningioma tissues normalized to that of Beta-actin. Relative mRNA expression of JAK1, STAT3, and VEGFa in a normal dura tissue, b grade I tissue, and c grade II tissue. Relative protein expression of JAK1, p-JAK1, STAT3, p-STAT3, and VEGF in d normal dura tissue, e grade I tissue, and f grade II tissue

Mentions: Among 30 grade I meningioma cases, JAK1 expression was detected in 11; STAT3 expression was detected in all JAK1-positive cases, and VEGFa expression was detected in all cases positive for both JAK1 and STAT3 and 1 case negative for both JAK1 and STAT3. JAK1 and STAT3 were detected at the same time in 8 out of the 10 grade II cases; VEGFa expression was found in 9 out of 10 grade II cases, including 8 cases positive for both JAK1 and STAT3. The frequencies of positivity and level of genes were high in grade I and II cases; no expression was found in normal dura tissues; high levels were found in grade II tissues (Table 1, Figs. 1, 2; P < 0.05).Table 1


Constitutive activation of signal transducer and activator of transcription 3 regulates expression of vascular endothelial growth factor in human meningioma differentiation.

Zhang MX, Zhao X, Wang ZG, Zhao WM, Wang YS - J. Cancer Res. Clin. Oncol. (2010)

Plots of gene expression from RT-PCR and Western blot analysis in normal dura and meningioma tissues normalized to that of Beta-actin. Relative mRNA expression of JAK1, STAT3, and VEGFa in a normal dura tissue, b grade I tissue, and c grade II tissue. Relative protein expression of JAK1, p-JAK1, STAT3, p-STAT3, and VEGF in d normal dura tissue, e grade I tissue, and f grade II tissue
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2874489&req=5

Fig2: Plots of gene expression from RT-PCR and Western blot analysis in normal dura and meningioma tissues normalized to that of Beta-actin. Relative mRNA expression of JAK1, STAT3, and VEGFa in a normal dura tissue, b grade I tissue, and c grade II tissue. Relative protein expression of JAK1, p-JAK1, STAT3, p-STAT3, and VEGF in d normal dura tissue, e grade I tissue, and f grade II tissue
Mentions: Among 30 grade I meningioma cases, JAK1 expression was detected in 11; STAT3 expression was detected in all JAK1-positive cases, and VEGFa expression was detected in all cases positive for both JAK1 and STAT3 and 1 case negative for both JAK1 and STAT3. JAK1 and STAT3 were detected at the same time in 8 out of the 10 grade II cases; VEGFa expression was found in 9 out of 10 grade II cases, including 8 cases positive for both JAK1 and STAT3. The frequencies of positivity and level of genes were high in grade I and II cases; no expression was found in normal dura tissues; high levels were found in grade II tissues (Table 1, Figs. 1, 2; P < 0.05).Table 1

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Shandong University School of Medicine, 44#, Wenhua Xi Road, 250012 Jinan, Shandong, People's Republic of China.

ABSTRACT

Purpose: 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.

Show MeSH
Related in: MedlinePlus