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
de 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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs de la prostate
/
Protéines de répression
/
Protéines nucléaires
/
Transduction du signal
/
Récepteurs aux androgènes
/
Phosphatidylinositol 3-kinases
/
Sérine-thréonine kinases TOR
/
Mutation
Type d'étude:
Prognostic_studies
Limites:
Animals
/
Humans
/
Male
Langue:
En
Journal:
Cancer Cell
Sujet du journal:
NEOPLASIAS
Année:
2017
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique