Jamie L Van Etten, Michael Nyquist, Yingming Li, Rendong Yang, Yeung Ho, Rachel Johnson, Olivia Ondigi, Daniel F Voytas, Christine Henzler, Scott M Dehm
Cancer research 2017 Oct 01Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant-specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3. Blocking this signal with morpholino technology or silencing of the polyadenylation factor CPSF1 caused a splice switch that inhibited expression of AR variants and blocked androgen-independent growth of CRPC cells. Our findings support the development of new therapies targeting the polyadenylation signal in AR intron 3 as a strategy to prevent expression of a broad array of AR variants in CRPC. Cancer Res; 77(19); 5228-35. ©2017 AACR. ©2017 American Association for Cancer Research.
Jamie L Van Etten, Michael Nyquist, Yingming Li, Rendong Yang, Yeung Ho, Rachel Johnson, Olivia Ondigi, Daniel F Voytas, Christine Henzler, Scott M Dehm. Targeting a Single Alternative Polyadenylation Site Coordinately Blocks Expression of Androgen Receptor mRNA Splice Variants in Prostate Cancer. Cancer research. 2017 Oct 01;77(19):5228-5235
PMID: 28928128
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