04(4.602)在弥散胶质瘤中AKT,NFKB和Stat3激活状态的分析.pdfVIP

Laboratory Investigation (2004) 84, 941–951 2004 USCAP, Inc All rights reserved 0023-6837/04 $30.00 Analysis of the activation status of Akt, NFjB, and Stat3 in human diffuse gliomas 1 1 1 2 2 Huamin Wang , Hua Wang , Wei Zhang , Helen J Huang , Warren SL Liao and Gregory N Fuller1 1Department of Pathology and 2Department of Biochemistry and Molecular Biology, Program in Genes and Development, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 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, NFjB, 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, NFjB, 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 NFjB and glioma grade. In contrast, only focal immunoreactivity for phospho-Stat3 was observed in o9% of high-grade gliomas. In addition, we observed a significant correlation between the activation of Akt and NFjB. Functional correlation between Akt activation and the activation of NFjB 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 NFjB-binding