Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism
Technical Report,01 Aug 2014,31 Jul 2016
Cedars-Sinai Medical Center Los Angeles United States
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This study provides novel links between the SAFB1, AR, EZH2, and ONECUT2 and genes that regulate sterol metabolism in castration resistant prostate cancer CRPC. Our findings to date have led to the working hypothesis that SAFB1 downregulation promotes a phenotype in CRPC that results in conservation of residual androgen in the tumor, thereby promoting an intracrine mechanism of AR activation. Interestingly, our data suggest that SAFB1 may cooperate with other proteins that act to deplete androgen from the tumor. This hypothesis is consistent with our bioinformatics analysis of thousands of RNA expression profiles from human prostate cancers that we have incorporated into this study. We found that about 13 of human prostate cancers, including primary tumors, exhibit an AR activation suppressed phenotype. We thus tested the hypothesis that SAFB1 is a critical mediator of this phenotype.