%0 Journal Article
%T BET bromodomain inhibition blocks the function of a critical AR-independent master regulator network in lethal prostate cancer
%J -
%D 2019
%R https://doi.org/10.1038/s41388-019-0815-5
%X BET bromodomain inhibitors block prostate cancer cell growth at least in part through c-Myc and androgen receptor (AR) suppression. However, little is known about other transcriptional regulators whose suppression contributes to BET bromodomain inhibitor anti-tumor activity. Moreover, the anti-tumor activity of BET bromodomain inhibition in AR-independent castration-resistant prostate cancers (CRPC), whose frequency is increasing, is also unknown. Herein, we demonstrate that BET bromodomain inhibition blocks growth of a diverse set of CRPC cell models, including those that are AR-independent or in which c-Myc is not suppressed. To identify transcriptional regulators whose suppression accounts for these effects, we treated multiple CRPC cell lines with the BET bromodomain inhibitor JQ1 and then performed RNA-sequencing followed by Master Regulator computational analysis. This approach identified several previously unappreciated transcriptional regulators that are highly expressed in CRPC and whose suppression, via both transcriptional or post-translational mechanisms, contributes to the anti-tumor activity of BET bromodomain inhibitors
%U https://www.nature.com/articles/s41388-019-0815-5