N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer.

Détails

ID Serval
serval:BIB_B22207EF398F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer.
Périodique
Cancer cell
Auteur(s)
Dardenne E., Beltran H., Benelli M., Gayvert K., Berger A., Puca L., Cyrta J., Sboner A., Noorzad Z., MacDonald T., Cheung C., Yuen K.S., Gao D., Chen Y., Eilers M., Mosquera J.M., Robinson B.D., Elemento O., Rubin M.A., Demichelis F., Rickman D.S.
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Statut éditorial
Publié
Date de publication
10/10/2016
Peer-reviewed
Oui
Volume
30
Numéro
4
Pages
563-577
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Résumé
The transition from castration-resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) has emerged as an important mechanism of treatment resistance. NEPC is associated with overexpression and gene amplification of MYCN (encoding N-Myc). N-Myc is an established oncogene in several rare pediatric tumors, but its role in prostate cancer progression is not well established. Integrating a genetically engineered mouse model and human prostate cancer transcriptome data, we show that N-Myc overexpression leads to the development of poorly differentiated, invasive prostate cancer that is molecularly similar to human NEPC. This includes an abrogation of androgen receptor signaling and induction of Polycomb Repressive Complex 2 signaling. Altogether, our data establishes N-Myc as an oncogenic driver of NEPC.
Mots-clé
Animals, Azepines/pharmacology, Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors, Enhancer of Zeste Homolog 2 Protein/genetics, Enhancer of Zeste Homolog 2 Protein/metabolism, Genes, myc, Heterografts, Humans, Male, Mice, Mice, Transgenic, N-Myc Proto-Oncogene Protein/biosynthesis, N-Myc Proto-Oncogene Protein/genetics, N-Myc Proto-Oncogene Protein/metabolism, Neuroendocrine Tumors/drug therapy, Neuroendocrine Tumors/genetics, Neuroendocrine Tumors/metabolism, Neuroendocrine Tumors/pathology, Prostatic Neoplasms/drug therapy, Prostatic Neoplasms/genetics, Prostatic Neoplasms/metabolism, Prostatic Neoplasms/pathology, Prostatic Neoplasms, Castration-Resistant/drug therapy, Prostatic Neoplasms, Castration-Resistant/genetics, Prostatic Neoplasms, Castration-Resistant/metabolism, Prostatic Neoplasms, Castration-Resistant/pathology, Protein Kinase Inhibitors/pharmacology, Pyrimidines/pharmacology, Signal Transduction, Transcription, Genetic, Aurora kinase A, EZH2, N-Myc, castration-resistant prostate adenocarcinoma, genetically engineered mouse, neuroendocrine prostate cancer, prostate cancer organoid
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/07/2020 11:24
Dernière modification de la notice
16/07/2020 8:43
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