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

First Author  Dardenne E Year  2016
Journal  Cancer Cell Volume  30
Issue  4 Pages  563-577
PubMed ID  27728805 Mgi Jnum  J:236713
Mgi Id  MGI:5806983 Doi  10.1016/j.ccell.2016.09.005
Citation  Dardenne E, et al. (2016) N-Myc Induces an EZH2-Mediated Transcriptional Program Driving Neuroendocrine Prostate Cancer. Cancer Cell 30(4):563-577
abstractText  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.
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