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mTOR pp 349-359 | Cite as

Inhibition of PI3K-Akt-mTOR Signaling in Glioblastoma by mTORC1/2 Inhibitors

Protocol
First Online:
Part of the Methods in Molecular Biology book series (MIMB, volume 821)

Abstract

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.

Key words

Glioblastoma PI3-kinase Akt:mTORC1 mTORC2 mTOR EGFR 
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Notes

Acknowledgments

We thank Zachary Knight, Benjamin Houseman, Morri Feldman, and Kevan Shokat for providing PI-103, PIK-90, and Ku-0063794. We acknowledge support from NIH grants PCA133091, NS055750, CA102321, CA097257, CA128583, CA148699 P01 CA081403, Burroughs Wellcome Fund, American Brain Tumor Association, The Brain Tumor Society, Accelerate Brain Cancer Cure; Alex’s Lemonade Stand, Children’s National Brain Tumor, Katie Dougherty, Pediatric Brain Tumor, Samuel G. Waxman and V Foundations.

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Copyright information

© Springer Science+Business Media, LLC  2012

Authors and Affiliations

  1. 1.Departments of Neurology, Pediatrics, Neurological Surgery and Brain Tumor Research Center, and Helen Diller Family Comprehensive Cancer CenterUniversity of CaliforniaSan FranciscoUSA

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