title: P-Akt expression distinguishes two types of malignant rhabdoid tumors.
abstract: Highly aggressive pediatric malignant rhabdoid tumors (MRT) arise in the kidney and central nervous system (CNS) with no curative treatment available. Multiple studies have shown that inactivation of the SNF5 tumor suppressor gene occurs in virtually all MRTs. However, few studies have addressed whether additional genetic events may contribute to MRT development. In this report, we demonstrate that phosphorylated Akt (P-Akt) is expressed in a subpopulation of cells in at least 10% of primary rhabdoid tumors as well as at high levels in three MRT cell lines. Similar to other high P-Akt expressing tumor cell lines, MRTs have decreased sensitivity to p21 induced growth arrest. Therefore, P-Akt expression may distinguish between two types of MRTs. Because drugs directed against the PI3-K/Akt have shown promise in clinical trials for other tumor types, they may prove useful for treatment of patients with P-Akt positive MRTs. P-Akt expression also provides a potential mechanistic link between these pediatric tumors and adult malignancies.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Aubri
authors.initials: A
authors.lastname: Charboneau
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chai
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jordan
authors.forename: William
authors.initials: W
authors.lastname: Funkhouser
authors.forename: Alexander
authors.initials: A
authors.lastname: Judkins
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Biegel
authors.forename: Bernard
authors.initials: B
authors.lastname: Weissman
mesh_terms: D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D018335:Rhabdoid Tumor / Q000145:classification* / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D050505:Mutant Proteins; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human