Aberrant Activation of a Gastrointestinal Transcriptional Circuit in Prostate Cancer Mediates Castration Resistance.
Cancer Cell
; 32(6): 792-806.e7, 2017 Dec 11.
Article
en En
| MEDLINE
| ID: mdl-29153843
ABSTRACT
Prostate cancer exhibits a lineage-specific dependence on androgen signaling. Castration resistance involves reactivation of androgen signaling or activation of alternative lineage programs to bypass androgen requirement. We describe an aberrant gastrointestinal-lineage transcriptome expressed in â¼5% of primary prostate cancer that is characterized by abbreviated response to androgen-deprivation therapy and in â¼30% of castration-resistant prostate cancer. This program is governed by a transcriptional circuit consisting of HNF4G and HNF1A. Cistrome and chromatin analyses revealed that HNF4G is a pioneer factor that generates and maintains enhancer landscape at gastrointestinal-lineage genes, independent of androgen-receptor signaling. In HNF4G/HNF1A-double-negative prostate cancer, exogenous expression of HNF4G at physiologic levels recapitulates the gastrointestinal transcriptome, chromatin landscape, and leads to relative castration resistance.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
/
Resistencia a Antineoplásicos
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Factor Nuclear 1-alfa del Hepatocito
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Factor Nuclear 4 del Hepatocito
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Neoplasias de la Próstata Resistentes a la Castración
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos