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N-Myc induces an EZH2-mediated transcriptional program driving Neuroendocrine Prostate Cancer

GSE86532 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 38 samples Submitted 2016/09/08 Platform GPL9185Platform GPL9052
Summary
The transition from castration resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) is emerging as an important mechanism of treatment resistance. NEPC are associated with over-expression and gene amplification of MYCN (encoding N-Myc). N-Myc is a bona fide driver oncogene in several rare tumor types, but its role in prostate cancer progression is not well established. Integrating a novel genetically engineered mouse model and human prostate cancer transcriptome data, we show that N-Myc over-expression leads to the development of poorly differentiated, invasive prostate cancer that is molecularly similar to human NEPC tumors which includes an abrogation of AR signaling and induction of Polycomb Repressive Complex 2 signaling and that N-Myc interacts with AR and this interaction depends on Enhancer of Zeste Homolog 2. Altogether, our data shows that N-Myc drives the neuroendocrine phenotype in prostate cancer.
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Also filed as BioProject PRJNA342161 and SRA study SRP087491. Searching any of these in the dataset finder brings you back here.

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