title: Suppression of T-cell lymphomagenesis in mice requires PTEN phosphatase activity.
abstract: Mice with T-cell-specific loss of the tumor suppressor gene PTEN early in T-cell ontogeny develop thymic lymphomas that invariably harbor a reciprocal translocation involving the T-cell receptor α/δ locus and c-myc, t(14;15). In addition to its known function as a lipid phosphatase opposing PI3K signaling, PTEN has also been described as playing a prominent role in promoting genomic stability. As a result, it has been uncertain which one(s) of these 2 separable features were required to block the development of lymphoma. Here, using a conditional model in which T cells selectively express 1 phosphatase-dead PTEN mutant (C124S) and maintain 1 null allele, we show that PTEN phosphatase activity is required for preventing the emergence of a malignant T-cell population harboring t(14;15), thus constituting a critical function of PTEN in preventing lymphomagenesis.
authors.affiliation: Department of Surgery and Center for Transplantation Sciences, Massachusetts General Hospital.
authors.forename: Ryan H
authors.initials: RH
authors.lastname: Newton
authors.affiliation: Department of Medicine, Brigham and Women's Hospital.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, and Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, and.
authors.forename: Antonella
authors.initials: A
authors.lastname: Papa
authors.affiliation: Department of Surgery and Center for Transplantation Sciences, Massachusetts General Hospital.
authors.forename: Greg H
authors.initials: GH
authors.lastname: Whitcher
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA.
authors.forename: Youn-Jung
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; and.
authors.forename: Catherine
authors.initials: C
authors.lastname: Yan
authors.affiliation: Cancer Research Institute, Beth Israel Deaconess Cancer Center, and Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, and.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
authors.affiliation: Department of Surgery and Center for Transplantation Sciences, Massachusetts General Hospital.
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000201:enzymology / Q000473:pathology; D002678:Chimera / Q000235:genetics / Q000378:metabolism; D033481:Chromosomes, Mammalian; D015972:Gene Expression Regulation, Neoplastic; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics*; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology* / Q000473:pathology; D013950:Thymus Gland / Q000201:enzymology / Q000473:pathology; D013953:Thymus Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic
chemical_list: D020033:Protein Isoforms; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse