Chromatin Occupancy of AR, BRD4, and H3K27Ac in MR42D Cells in response to Enzalutamide [RNA-seq]

To identify mechanisms that contribute to lineage plasticity and t-NEPC, we focused on enza-resistant cell lines with persistent AR expression that have features of lineage plasticity, including high expression of NEPC markers: the MR42D and MR42F cell lines. We cultured these enzalutamide resistant lines, which are usually maintained in medium with enzalutamide, without enzalutamide for 72 hors to "washout" the effects of enzalutamide, and then either enzalutamide or vehicle was added back to the growing media for 24 hours. Enzalutamide sensitive lines LNCaP and V16D were treated with either enzalutamide or vehicle for 24 hours. Enzalutamide reversibly increased expression neuronal markers in MR42D and MR42F cells, but not enza-sentitive LNCaP and V16D cells, suggesting that the AR may negatively regulate neuronal gene expression in these t-NEPC cells. Moreover, bromodomain inhibitors (BETi) ARV-771 and JQ1 reduced expression of NEPC target genes in MR42D cells. Four cell lines (MR42D, MR42F, LNCaP, and V16D) were treated with the AR-antagonist Enzalutamide (MDV) or Vehicle (DMSO) in biological triplicate. Separately, in culture media with enzalutamide present, the MR42D cell line was also treated with Bromodomain-inhibitors ARV771, JQ1, or Vehicle also in biological triplicates.