title: Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma.
abstract: Interferon-beta (IFN-β) is reported to augment anti-tumor effects by temozolomide in glioblastoma via down-regulation of MGMT. Promyelocytic leukemia (PML), a gene induced by IFN-β, is a tumor suppressor. Here, we report for the first time that in combination therapy, an IFN-β-induced increase in endogenous PML contributes to anti-tumor effects in p53 wild- and mutant glioma cells in a xenograft mice model. The increased PML promoted the accumulation of p73, a structural and functional homolog of p53, to fuse the coactivator Yes-associated-protein in the PML nuclear bodies. The adjuvant therapy targeted at PML may be a promising therapeutic strategy for glioblastoma.
authors.affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. tokazaki1978@sirius.ocn.ne.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okazaki
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Kageji
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kuwayama
authors.forename: Keiko T
authors.initials: KT
authors.lastname: Kitazato
authors.forename: Hideo
authors.initials: H
authors.lastname: Mure
authors.forename: Keijiro
authors.initials: K
authors.lastname: Hara
authors.forename: Ryoma
authors.initials: R
authors.lastname: Morigaki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Mizobuchi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Nagahiro
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001483:Base Sequence; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology; D000071156:Promyelocytic Leukemia Protein; D060888:Real-Time Polymerase Chain Reaction; D000077204:Temozolomide; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000502:physiology*; D015854:Up-Regulation; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000071156:Promyelocytic Leukemia Protein; C000606460:TP73 protein, human; D014157:Transcription Factors; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C070576:PML protein, human; D016899:Interferon-beta; D003606:Dacarbazine; D000077204:Temozolomide