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CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer.
Hwang, Justin H; Seo, Ji-Heui; Beshiri, Michael L; Wankowicz, Stephanie; Liu, David; Cheung, Alexander; Li, Ji; Qiu, Xintao; Hong, Andrew L; Botta, Ginevra; Golumb, Lior; Richter, Camden; So, Jonathan; Sandoval, Gabriel J; Giacomelli, Andrew O; Ly, Seav Huong; Han, Celine; Dai, Chao; Pakula, Hubert; Sheahan, Anjali; Piccioni, Federica; Gjoerup, Ole; Loda, Massimo; Sowalsky, Adam G; Ellis, Leigh; Long, Henry; Root, David E; Kelly, Kathleen; Van Allen, Eliezer M; Freedman, Matthew L; Choudhury, Atish D; Hahn, William C.
Afiliación
  • Hwang JH; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Seo JH; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Beshiri ML; Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Wankowicz S; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Liu D; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Cheung A; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Li J; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Qiu X; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Hong AL; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Botta G; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Golumb L; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Richter C; Dana-Farber Cancer Institute, Boston, MA, USA.
  • So J; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Sandoval GJ; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Giacomelli AO; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Ly SH; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Han C; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Dai C; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Pakula H; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Sheahan A; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Piccioni F; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Gjoerup O; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Loda M; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Sowalsky AG; Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Ellis L; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Brigham and Women's Hospital, Boston, MA, USA.
  • Long H; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Root DE; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Kelly K; Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
  • Van Allen EM; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Freedman ML; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Choudhury AD; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Hahn WC; Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Brigham and Women's Hospital, Boston, MA, USA. Electronic address: william_hahn@dfci.harvard.edu.
Cell Rep ; 29(8): 2355-2370.e6, 2019 11 19.
Article en En | MEDLINE | ID: mdl-31747605
ABSTRACT
Androgen-receptor (AR) inhibitors, including enzalutamide, are used for treatment of all metastatic castration-resistant prostate cancers (mCRPCs). However, some patients develop resistance or never respond. We find that the transcription factor CREB5 confers enzalutamide resistance in an open reading frame (ORF) expression screen and in tumor xenografts. CREB5 overexpression is essential for an enzalutamide-resistant patient-derived organoid. In AR-expressing prostate cancer cells, CREB5 interactions enhance AR activity at a subset of promoters and enhancers upon enzalutamide treatment, including MYC and genes involved in the cell cycle. In mCRPC, we found recurrent amplification and overexpression of CREB5. Our observations identify CREB5 as one mechanism that drives resistance to AR antagonists in prostate cancers.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Proteína de Unión al Elemento de Respuesta al AMP Cíclico / Antagonistas de Receptores Androgénicos Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Asunto principal: Proteína de Unión al Elemento de Respuesta al AMP Cíclico / Antagonistas de Receptores Androgénicos Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos