BET bromodomain inhibition blocks the function of a critical AR-independent master regulator network in lethal prostate cancer.
Oncogene
; 38(28): 5658-5669, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-30996246
ABSTRACT
BET bromodomain inhibitors block prostate cancer cell growth at least in part through c-Myc and androgen receptor (AR) suppression. However, little is known about other transcriptional regulators whose suppression contributes to BET bromodomain inhibitor anti-tumor activity. Moreover, the anti-tumor activity of BET bromodomain inhibition in AR-independent castration-resistant prostate cancers (CRPC), whose frequency is increasing, is also unknown. Herein, we demonstrate that BET bromodomain inhibition blocks growth of a diverse set of CRPC cell models, including those that are AR-independent or in which c-Myc is not suppressed. To identify transcriptional regulators whose suppression accounts for these effects, we treated multiple CRPC cell lines with the BET bromodomain inhibitor JQ1 and then performed RNA-sequencing followed by Master Regulator computational analysis. This approach identified several previously unappreciated transcriptional regulators that are highly expressed in CRPC and whose suppression, via both transcriptional or post-translational mechanisms, contributes to the anti-tumor activity of BET bromodomain inhibitors.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Receptores Androgênicos
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Proteínas de Ciclo Celular
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Neoplasias de Próstata Resistentes à Castração
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article