PMID- 22125077 OWN - NLM STAT- MEDLINE DCOM- 20120316 LR - 20211203 IS - 1940-6029 (Electronic) IS - 1064-3745 (Print) IS - 1064-3745 (Linking) VI - 821 DP - 2012 TI - Inhibition of PI3K-Akt-mTOR signaling in glioblastoma by mTORC1/2 inhibitors. PG - 349-59 LID - 10.1007/978-1-61779-430-8_22 [doi] AB - Amplification of the gene encoding the epidermal growth factor receptor (EGFR) occurs commonly in glioblastoma (GBM), leading to activation of downstream kinases, including phosphatidylinositol 3'-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR). A serine-threonine kinase, mTOR controls cell growth by regulating mRNA translation, metabolism, and autophagy; acting as both a downstream effector and upstream regulator of PI3K. These signaling functions are distributed between at least two distinct complexes, mTORC1 and mTORC2 with respect to pathway specificity. We have investigated mTOR signaling in glioma cells with the allosteric mTORC1 inhibitor rapamycin, the mTORC1/2 inhibitor Ku-0063794, a dual PI3K/mTORC1/2 kinase inhibitor PI-103, and siRNA against raptor, rictor, or mTOR, and evaluated the value of mTOR inhibitors for the treatment of glioblastoma. FAU - Fan, Qi-Wen AU - Fan QW AD - Department of Neurology, University of California, San Francisco, CA, USA. qiwen.fan@ucsf.edu FAU - Weiss, William A AU - Weiss WA LA - eng GR - R01 CA102321/CA/NCI NIH HHS/United States GR - R01 CA133091/CA/NCI NIH HHS/United States GR - CA128583/CA/NCI NIH HHS/United States GR - P01 CA081403/CA/NCI NIH HHS/United States GR - CA148699/CA/NCI NIH HHS/United States GR - P50 CA097257/CA/NCI NIH HHS/United States GR - R01 CA148699/CA/NCI NIH HHS/United States GR - CA097257/CA/NCI NIH HHS/United States GR - T32 CA128583/CA/NCI NIH HHS/United States GR - NS055750/NS/NINDS NIH HHS/United States GR - PCA133091/PHS HHS/United States GR - R01 NS055750/NS/NINDS NIH HHS/United States GR - CA102321/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Methods Mol Biol JT - Methods in molecular biology (Clifton, N.J.) JID - 9214969 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (CRTC2 protein, human) RN - 0 (Carrier Proteins) RN - 0 (Furans) RN - 0 (Morpholines) RN - 0 (Multiprotein Complexes) RN - 0 (PI103) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Proteins) RN - 0 (Pyridines) RN - 0 (Pyrimidines) RN - 0 (RICTOR protein, human) RN - 0 (RNA, Small Interfering) RN - 0 (RPTOR protein, human) RN - 0 (Rapamycin-Insensitive Companion of mTOR Protein) RN - 0 (Regulatory-Associated Protein of mTOR) RN - 0 (Transcription Factors) RN - 81HJG228AB (Ku 0063794) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adaptor Proteins, Signal Transducing/antagonists & inhibitors/genetics MH - Carrier Proteins/antagonists & inhibitors/genetics MH - Cell Line, Tumor MH - ErbB Receptors/metabolism MH - Furans/pharmacology MH - Gene Expression Regulation, Neoplastic/drug effects MH - Glioblastoma/*enzymology MH - Humans MH - Mechanistic Target of Rapamycin Complex 1 MH - Morpholines/pharmacology MH - Multiprotein Complexes MH - Oncogene Protein v-akt/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Protein Kinase Inhibitors/*pharmacology MH - Proteins/*antagonists & inhibitors MH - Pyridines/pharmacology MH - Pyrimidines/pharmacology MH - RNA, Small Interfering/genetics/metabolism MH - Rapamycin-Insensitive Companion of mTOR Protein MH - Regulatory-Associated Protein of mTOR MH - Signal Transduction MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases MH - Transcription Factors/*antagonists & inhibitors PMC - PMC3402221 MID - NIHMS391829 EDAT- 2011/11/30 06:00 MHDA- 2012/03/17 06:00 PMCR- 2013/01/01 CRDT- 2011/11/30 06:00 PHST- 2011/11/30 06:00 [entrez] PHST- 2011/11/30 06:00 [pubmed] PHST- 2012/03/17 06:00 [medline] PHST- 2013/01/01 00:00 [pmc-release] AID - 10.1007/978-1-61779-430-8_22 [doi] PST - ppublish SO - Methods Mol Biol. 2012;821:349-59. doi: 10.1007/978-1-61779-430-8_22.