TY - JOUR
T1 - Analysis of the activation status of Akt, NFκB, and Stat3 in human diffuse gliomas
AU - Wang, Huamin
AU - Wang, Hua
AU - Zhang, Wei
AU - Huang, Helen J.
AU - Liao, Warren S.L.
AU - Fuller, Gregory N.
PY - 2004/8
Y1 - 2004/8
N2 - Loss of phosphatase and tensin homolog (PTEN) and amplification of the epidermal growth factor receptor (EGFR) gene contribute to the progression of gliomas. As downstream targets of the PTEN and EGFR signaling pathways, Akt, NFκB, and signal transducer and activator of transcription-3 (Stat3) have been shown to play important roles in the control of cell proliferation, apoptosis, and oncogenesis. We examined the activation status of Akt, NFκB, and Stat3 in 259 diffuse gliomas using tissue microarrays and immunohistochemistry, and evaluated their association with glioma grade. We observed significant positive correlations between the activation status of Akt and NFκB and glioma grade. In contrast, only focal immunoreactivity for phospho-Stat3 was observed in <9% of high-grade gliomas. In addition, we observed a significant correlation between the activation of Akt and NFκB. Functional correlation between Akt activation and the activation of NFκB was confirmed in U251MG GBM cells in which inhibition of Akt activation either by stable expression of PTEN or by the PI3-kinase inhibitors, wortmannin and LY294002, led to a concomitant decrease in NFκB-binding activity. Thus, our results demonstrate that constitutive activation of Akt and NFκB, but not Stat3, contributes significantly to the progression of diffuse gliomas, and activation of Akt may lead to NFκB activation in high-grade gliomas.
AB - Loss of phosphatase and tensin homolog (PTEN) and amplification of the epidermal growth factor receptor (EGFR) gene contribute to the progression of gliomas. As downstream targets of the PTEN and EGFR signaling pathways, Akt, NFκB, and signal transducer and activator of transcription-3 (Stat3) have been shown to play important roles in the control of cell proliferation, apoptosis, and oncogenesis. We examined the activation status of Akt, NFκB, and Stat3 in 259 diffuse gliomas using tissue microarrays and immunohistochemistry, and evaluated their association with glioma grade. We observed significant positive correlations between the activation status of Akt and NFκB and glioma grade. In contrast, only focal immunoreactivity for phospho-Stat3 was observed in <9% of high-grade gliomas. In addition, we observed a significant correlation between the activation of Akt and NFκB. Functional correlation between Akt activation and the activation of NFκB was confirmed in U251MG GBM cells in which inhibition of Akt activation either by stable expression of PTEN or by the PI3-kinase inhibitors, wortmannin and LY294002, led to a concomitant decrease in NFκB-binding activity. Thus, our results demonstrate that constitutive activation of Akt and NFκB, but not Stat3, contributes significantly to the progression of diffuse gliomas, and activation of Akt may lead to NFκB activation in high-grade gliomas.
KW - Akt
KW - Glioma
KW - NFMκB
KW - Stat3
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U2 - 10.1038/labinvest.3700123
DO - 10.1038/labinvest.3700123
M3 - Article
C2 - 15184909
AN - SCOPUS:3543056884
SN - 0023-6837
VL - 84
SP - 941
EP - 951
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 8
ER -