Aberrant Wnt/beta-catenin signaling contributes to the development of many cancers, including glial tumorigenesis. While cross talk between the Wnt/beta-catenin and PI3K/AKT signaling pathways has been proposed, the impact of PI3K/AKT inhibition on beta-catenin signaling in glioma remains unknown. In the present study, we report decreased cell proliferation and invasive ability upon the LY294002-induced inhibition of PI3K in both U251 and LN229 human glioblastoma cells in vitro. Pharmacologic inhibition of PI3K resulted in the downregulation of several members of the beta-catenin pathway, including Fra-1, c-Myc, and cyclin D1. Downregulation impacted beta-catenin-mediated transcription, as LY294002 decreased beta-catenin/TCF transcriptional activity, determined by the reporter assay. Similar results were observed in vivo, as intratumoral injection of LY294002 downregulated the expression of the components of the beta-catenin pathway and delayed tumor growth in nude mice harboring subcutaneous LN229 xenografts. These results suggest that the PI3K/AKT signaling pathway regulates glioma cell proliferation, in part via repression of the Wnt/beta-catenin pathway. (C) 2010 Elsevier B.V. All rights reserved.
基金：
National Key Project of Science and Technology Supporting Programs of China [2007BAI05B08]; China National Natural Scientific FundNational Natural Science Foundation of China [30772238, 30772231, 30971136]; Program for New Century Excellent Talents in UniversityProgram for New Century Excellent Talents in University (NCET) [NCET-07-0615]; Tianjin Science and Technology Committee [09JCZDJC17600]
第一作者机构：[2]Tianjin Med Univ, Dept Neurosurg, Lab Neurooncol, Key Lab Neurotrauma Variat & Regenerat,Minist Edu, Tianjin 300052, Peoples R China;[5]Tianjin Municipal Govt, Tianjin 300052, Peoples R China
通讯作者：
通讯机构：[1]Capital Med Univ, Dept Neurosurg, Tiantan Hosp, Beijing 100050, Peoples R China;
推荐引用方式(GB/T 7714)：
Han Lei,Yang Yang,Yue Xiao,et al.Inactivation of PI3K/AKT signaling inhibits glioma cell growth through modulation of beta-catenin-mediated transcription[J].BRAIN RESEARCH.2010,1366:9-17.doi:10.1016/j.brainres.2010.09.097.
APA：
Han, Lei,Yang, Yang,Yue, Xiao,Huang, Kai,Liu, Xiaomin...&Kang, Chunsheng.(2010).Inactivation of PI3K/AKT signaling inhibits glioma cell growth through modulation of beta-catenin-mediated transcription.BRAIN RESEARCH,1366,
MLA：
Han, Lei,et al."Inactivation of PI3K/AKT signaling inhibits glioma cell growth through modulation of beta-catenin-mediated transcription".BRAIN RESEARCH 1366.(2010):9-17
