Pten/Pi3k/Akt Pathway Regulates The Side Population Phenotype And Abcg2 Activity In Glioma Tumor Stem Cells

Gliomas are the most common adult primary brain tumors; the majority of these tumors remain difficult to treat due to resistance to cytotoxic therapy. The resistance phenotype arises in large part due to the expression of ABC transporters that efflux drugs out of cells. Such cells also possess the ability to exclude Hoechst dye, allowing their sorting into a specific population referred to as the side population (SP). In this study, we isolated SP cells from normal mouse brain and PDGF-induced gliomas that highly express the transporter ABCG2. While the SP of the normal brain consisted entirely of endothelial cells, the SP fraction isolated from tumors was enriched in tumor cells. Characterization of these cells highlighted the expression of the progenitor marker nestin, the oligodendrocyte progenitor marker A2B5 and, to a lesser extent, CD133. In culture, SP cells formed more neurospheres than those of the main …