| First Author | Akamatsu S | Year | 2015 |
| Journal | Cell Rep | Volume | 12 |
| Issue | 6 | Pages | 922-36 |
| PubMed ID | 26235627 | Mgi Jnum | J:232893 |
| Mgi Id | MGI:5780387 | Doi | 10.1016/j.celrep.2015.07.012 |
| Citation | Akamatsu S, et al. (2015) The Placental Gene PEG10 Promotes Progression of Neuroendocrine Prostate Cancer. Cell Rep 12(6):922-36 |
| abstractText | More potent targeting of the androgen receptor (AR) in advanced prostate cancer is driving an increased incidence of neuroendocrine prostate cancer (NEPC), an aggressive and treatment-resistant AR-negative variant. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. We modeled the development of NEPC from conventional prostatic adenocarcinoma using a patient-derived xenograft and found that the placental gene PEG10 is de-repressed during the adaptive response to AR interference and subsequently highly upregulated in clinical NEPC. We found that the AR and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at distinct stages of NEPC development. In vitro, PEG10 promoted cell-cycle progression from G0/G1 in the context of TP53 loss and regulated Snail expression via TGF-beta signaling to promote invasion. Taken together, these findings show the mechanistic relevance of RB1 and TP53 loss in NEPC and suggest PEG10 as a NEPC-specific target. |
