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TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.
Groner, Anna C; Cato, Laura; de Tribolet-Hardy, Jonas; Bernasocchi, Tiziano; Janouskova, Hana; Melchers, Diana; Houtman, René; Cato, Andrew C B; Tschopp, Patrick; Gu, Lei; Corsinotti, Andrea; Zhong, Qing; Fankhauser, Christian; Fritz, Christine; Poyet, Cédric; Wagner, Ulrich; Guo, Tiannan; Aebersold, Ruedi; Garraway, Levi A; Wild, Peter J; Theurillat, Jean-Philippe; Brown, Myles.
Afiliação
  • Groner AC; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Cato L; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • de Tribolet-Hardy J; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Bernasocchi T; Institute of Oncology Research, Bellinzona 6500, Switzerland.
  • Janouskova H; Institute of Oncology Research, Bellinzona 6500, Switzerland.
  • Melchers D; PamGene International, Den Bosch 521HH, the Netherlands.
  • Houtman R; PamGene International, Den Bosch 521HH, the Netherlands.
  • Cato ACB; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76344 Eggenstein-Leopoldshafen, Germany.
  • Tschopp P; Department of Genetics, Harvard Medical School, Boston, MA 02215, USA.
  • Gu L; Division of Newborn Medicine, Children's Hospital Boston and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA.
  • Corsinotti A; MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH16 4UU, UK; Laboratory Animal Resource Center, Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibarak
  • Zhong Q; Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
  • Fankhauser C; Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland; Department of Urology, University Hospital Zurich, Zurich 8091, Switzerland.
  • Fritz C; Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
  • Poyet C; Department of Urology, University Hospital Zurich, Zurich 8091, Switzerland.
  • Wagner U; Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
  • Guo T; Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich 8093, Switzerland.
  • Aebersold R; Department of Biology, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich 8093, Switzerland; Faculty of Science, University of Zurich, Zurich 8057, Switzerland.
  • Garraway LA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Wild PJ; Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
  • Theurillat JP; Institute of Oncology Research, Bellinzona 6500, Switzerland; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne 1011, Switzerland. Electronic address: jeanp_theurillat@ior.iosi.ch.
  • Brown M; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: myles_brown@dfci.harvard.edu.
Cancer Cell ; 29(6): 846-858, 2016 06 13.
Article em En | MEDLINE | ID: mdl-27238081
ABSTRACT
Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in speckle-type POZ protein (SPOP) stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly upregulated in CRPC. Expression of TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 gene signature predict disease recurrence. Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR-interacting motif are essential to support proliferation. These data provide a rationale for therapeutic TRIM24 targeting in SPOP mutant and CRPC patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Proteínas Repressoras / Proteínas Nucleares / Proteínas de Transporte / Receptores Androgênicos / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Proteínas Repressoras / Proteínas Nucleares / Proteínas de Transporte / Receptores Androgênicos / Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos