Oncotarget

Research Papers:

Establishment of a neuroendocrine prostate cancer model driven by the RNA splicing factor SRRM4

Yinan Li, Ruiqi Chen, Mary Bowden, Fan Mo, Yen-Yi Lin, Martin Gleave, Colin Collins and Xuesen Dong _

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Oncotarget. 2017; 8:66878-66888. https://doi.org/10.18632/oncotarget.19916

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Abstract

Yinan Li1, Ruiqi Chen1, Mary Bowden1, Fan Mo1, Yen-Yi Lin1, Martin Gleave1, Colin Collins1 and Xuesen Dong1

1 Department of Urologic Sciences, Vancouver Prostate Centre, The University of British Columbia, Vancouver, Canada

Correspondence to:

Xuesen Dong, email:

Keywords: neuroendocrine prostate cancer, cell/tumor models, SRRM4, RNA splicing

Received: June 30, 2017 Accepted: July 06, 2017 Published: August 03, 2017

Abstract

Neuroendocrine prostate cancer (NEPC) is becoming more prevalent as more potent androgen receptor (AR) pathway inhibitors are applied to patients with metastatic tumors. However, there are limited cell and xenograft models currently available, hindering the investigation of signal pathways involved in regulating NEPC progression and the design of high throughput screening assays for inhibitors to treat NEPC patients. Here, we report an NEPC model, LnNE, that is derived from prostate adenocarcinoma cells and has global similarity in transcription and RNA splicing to tumors from NEPC patients. LnNE xenografts are castrate-resistant and highly aggressive. Its tumor take is ~3-5 weeks and tumor doubling time is ~2-3 weeks. LnNE expresses multiple neuroendocrine markers, preserves AR expression, but is PSA negative. Its neuroendocrine phenotype cannot be reversed by androgen treatment. LnNE cells grow as multi-cellular spheroids under 2-dimensional culture conditions similar to the NEPC cell line NCI-H660, but have higher proliferation rate and are easier to be transfected. LnNE cells can also adapt to 3-dimensional culture conditions in a 96-plate format, allowing high throughput screening assays. In summary, the LnNE model is useful to study the mechanisms of NEPC progression and to discover potential therapies for NEPC.


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