| Literature DB >> 27728805 |
Etienne Dardenne1, Himisha Beltran2, Matteo Benelli3, Kaitlyn Gayvert4, Adeline Berger1, Loredana Puca5, Joanna Cyrta6, Andrea Sboner7, Zohal Noorzad1, Theresa MacDonald1, Cynthia Cheung1, Ka Shing Yuen1, Dong Gao8, Yu Chen9, Martin Eilers10, Juan-Miguel Mosquera6, Brian D Robinson6, Olivier Elemento11, Mark A Rubin12, Francesca Demichelis13, David S Rickman14.
Abstract
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.Entities:
Keywords: Aurora kinase A; EZH2; N-Myc; castration-resistant prostate adenocarcinoma; genetically engineered mouse; neuroendocrine prostate cancer; prostate cancer organoid
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Year: 2016 PMID： 27728805 PMCID： PMC5540451 DOI： 10.1016/j.ccell.2016.09.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743