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The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer.
Magnani, Luca; Patten, Darren K; Nguyen, Van T M; Hong, Sung-Pil; Steel, Jennifer H; Patel, Naina; Lombardo, Ylenia; Faronato, Monica; Gomes, Ana R; Woodley, Laura; Page, Karen; Guttery, David; Primrose, Lindsay; Fernandez Garcia, Daniel; Shaw, Jacqui; Viola, Patrizia; Green, Andrew; Nolan, Christopher; Ellis, Ian O; Rakha, Emad A; Shousha, Sami; Lam, Eric W-F; Gyorffy, Balázs; Lupien, Mathieu; Coombes, R Charles.
Afiliación
  • Magnani L; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Patten DK; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Nguyen VT; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Hong SP; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Steel JH; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Patel N; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Lombardo Y; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Faronato M; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Gomes AR; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Woodley L; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Page K; Department of Cancer Studies, University of Leicester, Leicester, UK.
  • Guttery D; Department of Cancer Studies, University of Leicester, Leicester, UK.
  • Primrose L; Department of Cancer Studies, University of Leicester, Leicester, UK.
  • Fernandez Garcia D; Department of Cancer Studies, University of Leicester, Leicester, UK.
  • Shaw J; Department of Cancer Studies, University of Leicester, Leicester, UK.
  • Viola P; Laboratory of Medicine, Histopathology Department, Royal Brompton Hospital, London, UK.
  • Green A; Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Budapest, HU.
  • Nolan C; Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Budapest, HU.
  • Ellis IO; Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Budapest, HU.
  • Rakha EA; Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Budapest, HU.
  • Shousha S; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Lam EW; Department of Surgery and Cancer, Imperial College London, London, UK.
  • Gyorffy B; MTA TTK Lendület Cancer Biomarker Research Group, 2nd Department of Pediatrics, Semmelweis University and MTA-SE Pediatrics and Nephrology Research Group, Budapest, HU.
  • Lupien M; The Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Coombes RC; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Oncotarget ; 6(26): 21878-91, 2015 Sep 08.
Article en En | MEDLINE | ID: mdl-26215677
Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Proteínas Proto-Oncogénicas / Receptor alfa de Estrógeno / Proteínas de Unión al ADN Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Oncotarget Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Proteínas Proto-Oncogénicas / Receptor alfa de Estrógeno / Proteínas de Unión al ADN Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Oncotarget Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos