SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling.
Cancer Cell
; 31(3): 436-451, 2017 03 13.
Article
em En
| MEDLINE
| ID: mdl-28292441
ABSTRACT
Recurrent point mutations in SPOP define a distinct molecular subclass of prostate cancer. Here, we describe a mouse model showing that mutant SPOP drives prostate tumorigenesis in vivo. Conditional expression of mutant SPOP in the prostate dramatically altered phenotypes in the setting of Pten loss, with early neoplastic lesions (high-grade prostatic intraepithelial neoplasia) with striking nuclear atypia and invasive, poorly differentiated carcinoma. In mouse prostate organoids, mutant SPOP drove increased proliferation and a transcriptional signature consistent with human prostate cancer. Using these models and human prostate cancer samples, we show that SPOP mutation activates both PI3K/mTOR and androgen receptor signaling, effectively uncoupling the normal negative feedback between these two pathways.
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MEDLINE
Assunto principal:
Neoplasias da Próstata
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Proteínas Repressoras
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Proteínas Nucleares
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Transdução de Sinais
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Receptores Androgênicos
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Fosfatidilinositol 3-Quinases
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Serina-Treonina Quinases TOR
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Mutação
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article