Journal article
PTEN/PI3K/Akt Pathway Regulates the Side Population Phenotype and ABCG2 Activity in Glioma Tumor Stem-like Cells
Cell stem cell, v 4(3), pp 226-235
06 Mar 2009
PMID: 19265662
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In normal brain, the side population (SP) phenotype is generated by ABC transporter activity and identifies stem cell and endothelial cell subpopulations by dye exclusion. By drug efflux, the ABCG2 transporter provides chemoresistance in stem cells and contributes to the blood brain barrier (BBB) when active in endothelial cells. We investigated the SP phenotype of mouse and human gliomas. In glioma endothelial cells, ABC transporter function is impaired, corresponding to disruption of the BBB in these tumors. By contrast, the SP phenotype is increased in nonendothelial cells that form neurospheres and are highly tumorigenic. In this cell population, Akt, but not its downstream target mTOR, regulates ABCG2 activity, and loss of PTEN increases the SP. This Akt-induced ABCG2 activation results from its transport to the plasma membrane. Temozolomide, the standard treatment of gliomas, although not an ABCG2 substrate, increases the SP in glioma cells, especially in cells missing PTEN.
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Details
- Title
- PTEN/PI3K/Akt Pathway Regulates the Side Population Phenotype and ABCG2 Activity in Glioma Tumor Stem-like Cells
- Creators
- Anne-Marie Bleau - Memorial Sloan Kettering Cancer CenterDolores Hambardzumyan - Memorial Sloan Kettering Cancer CenterTatsuya Ozawa - Memorial Sloan Kettering Cancer CenterElena I. Fomchenko - Memorial Sloan Kettering Cancer CenterJason T. Huse - Memorial Sloan Kettering Cancer CenterCameron W. Brennan - Memorial Sloan Kettering Cancer CenterEric C. Holland - Memorial Sloan Kettering Cancer Center
- Publication Details
- Cell stem cell, v 4(3), pp 226-235
- Publisher
- Elsevier
- Number of pages
- 10
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurology
- Web of Science ID
- WOS:000264369300013
- Scopus ID
- 2-s2.0-60849117508
- Other Identifier
- 991022004877904721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cell & Tissue Engineering
- Cell Biology