Pten signaling in gliomas

Abstract

In 1997, the PTEN gene (phosphatase and tensin homolog deleted onchromosome 10) was identified as a tumor suppressor gene on the long arm ofchromosome 10. Since then, important progress has been made with respect tothe understanding of the role of the Pten protein in the normal development ofthe brain as well as in the molecular pathogenesis of human gliomas. Thisreview summarizes the current state of the art concerning the involvement ofaberrant Pten function in the development of different biologic features ofmalignant gliomas, such as loss of cell-cycle control and uncontrolled cellproliferation, escape from apoptosis, brain invasion, and aberrantneoangiogenesis. Most of the tumor-suppressive properties of Pten aredependent on its lipid phosphatase activity, which inhibits thephosphatidylinositol-3'-kinase (PI3K)/Akt signaling pathway throughdephosphorylation of phosphatidylinositol-(3,4,5)-tri phosphate. Theadditional function of Pten as a dual-specificity protein phosphatase may alsoplay a role in glioma pathogenesis. Besides the wealth of data elucidating thefunctional roles of Pten, recent studies suggest a diagnostic significance ofPTEN gene alterations as a molecular marker for poor prognosis inanaplastic astrocytomas and anaplastic oligodendrogliomas. Furthermore, thepossibility of selective targeting of PTEN mutant tumor cells byspecific pharmacologic inhibitors of members of the Pten/PI3K/Akt pathwayopens up new perspectives for a targeted molecular therapy of malignantgliomas.