Analysis of the activation status of Akt, NFκB, and Stat3 in human diffuse gliomas

摘要: Loss of phosphatase and tensin homolog (PTEN) amplification the epidermal growth factor receptor (EGFR) gene contribute to progression gliomas. As downstream targets PTEN EGFR signaling pathways, Akt, NFκB, signal transducer activator transcription-3 (Stat3) have been shown play important roles in control cell proliferation, apoptosis, oncogenesis. We examined activation status Stat3 259 diffuse gliomas using tissue microarrays immunohistochemistry, evaluated their association with glioma grade. observed significant positive correlations between Akt NFκB In contrast, only focal immunoreactivity for phospho-Stat3 was <9% high-grade addition, we a correlation NFκB. Functional confirmed U251MG GBM cells which inhibition either by stable expression or PI3-kinase inhibitors, wortmannin LY294002, led concomitant decrease NFκB-binding activity. Thus, our results demonstrate that constitutive but not Stat3, contributes significantly gliomas, may lead