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

被引：414

作者：

Dardenne, Etienne ^{[1
]}

Beltran, Himisha ^{[2
,3
,4
]}

Benelli, Matteo ^{[5
]}

Gayvert, Kaitlyn ^{[6
,7
,8
]}

Berger, Adeline ^{[1
]}

Puca, Loredana ^{[4
]}

Cyrta, Joanna ^{[1
,4
]}

Sboner, Andrea ^{[1
,4
,6
,7
,8
]}

Noorzad, Zohal ^{[1
]}

MacDonald, Theresa ^{[1
]}

Cheung, Cynthia ^{[1
]}

Yuen, Ka Shing ^{[1
]}

Gao, Dong

Chen, Yu ^{[3
,9
,10
]}

Eilers, Martin ^{[11
,12
]}

Mosquera, Juan-Miguel ^{[1
,4
]}

Robinson, Brian D. ^{[1
,4
]}

Elemento, Olivier ^{[2
,4
,6
]}

Rubin, Mark A. ^{[1
,2
,4
,6
]}

Demichelis, Francesca ^{[4
,5
]}

Rickman, David S. ^{[1
,2
,4
]}

机构：

[1] Weill Cornell Med, Dept Pathol & Lab Med, New York, NY 10065 USA

[2] Weill Cornell Med, Meyer Canc Ctr, New York, NY 10065 USA

[3] Weill Cornell Med, Dept Med, New York, NY 10065 USA

[4] New York Presbyterian Hosp, Weill Cornell Med, Englander Inst Precis Med, New York, NY 10065 USA

[5] Univ Trento, Ctr Integrat Biol, I-38123 Trento, Italy

[6] Weill Cornell Med, Inst Computat Biomed, Dept Physiol & Biophys, New York, NY 10065 USA

[7] Mem Sloan Kettering Canc Ctr, Weill Cornell Med, Triinst Training Program Computat Biol & Med, New York, NY 10065 USA

[8] Cornell Univ, Ithaca, NY 14853 USA

[9] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[10] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[11] Univ Wurzburg, Theodor Boveri Inst, D-97074 Wurzburg, Germany

[12] Univ Wurzburg, Bioctr, Comprehens Canc Ctr Mainfranken, D-97074 Wurzburg, Germany

来源：

CANCER CELL | 2016年 / 30卷 / 04期

基金：

欧洲研究理事会;

关键词：

SMALL-CELL CARCINOMA; MOUSE MODEL; DIFFERENTIATION; PTEN; ADENOCARCINOMA; IDENTIFICATION; REARRANGEMENT; INACTIVATION; GENOMICS; PROTEIN;

D O I：

10.1016/j.ccell.2016.09.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 off Polycomb Repressive Complex 2 signaling. Altogether, our data establishes N-Myc as an oncogenic driver of NEPC.

引用

页码：563 / 577

页数：15

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