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The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer.
Sharma, Naomi L; Massie, Charlie E; Butter, Falk; Mann, Matthias; Bon, Helene; Ramos-Montoya, Antonio; Menon, Suraj; Stark, Rory; Lamb, Alastair D; Scott, Helen E; Warren, Anne Y; Neal, David E; Mills, Ian G.
Afiliación
  • Sharma NL; Uro-oncology Research Group, CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK Department of Urology, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
  • Massie CE; Uro-oncology Research Group, CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
  • Butter F; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
  • Mann M; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
  • Bon H; Uro-oncology Research Group, CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
  • Ramos-Montoya A; Uro-oncology Research Group, CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
  • Menon S; Department of Bioinformatics, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
  • Stark R; Department of Bioinformatics, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
  • Lamb AD; Uro-oncology Research Group, CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
  • Scott HE; Uro-oncology Research Group, CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
  • Warren AY; Department of Pathology, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
  • Neal DE; Uro-oncology Research Group, CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK Department of Urology, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Hills Road
  • Mills IG; Uro-oncology Research Group, CRUK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK Prostate Cancer Research Group, Centre for Molecular Medicine (Norway), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Gaustadalleen 21,
Nucleic Acids Res ; 42(10): 6256-69, 2014 Jun.
Article en En | MEDLINE | ID: mdl-24753418
ABSTRACT
In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Receptores Androgénicos / Factor de Transcripción de la Proteína de Unión a GA Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nucleic Acids Res Año: 2014 Tipo del documento: Article País de afiliación: Reino Unido
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Receptores Androgénicos / Factor de Transcripción de la Proteína de Unión a GA Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nucleic Acids Res Año: 2014 Tipo del documento: Article País de afiliación: Reino Unido