PLX270244

GSE125245: CDK7 inhibition suppresses Castration-Resistant Prostate Cancer through MED1 inactivation

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

We performed RNA-seq and ChIP-seq in three prostate cell lines (VCaP, LNCaP and DU145) to ascertain the role of the mediator complex MED1 in AR signaling. Upon androgen stimulation, MED1 undergoes phosphorylation by CDK7 and physically engages with AR at super-enhancer sites, which is essential for AR-mediated transcription. The CDK7 specific inhibitor THZ1 blunts AR-dependent neoplastic growth by preventing the co-recruitment of AR/MED1 in a genome-wide fashion, and reverts the enzalutamide resistance characterized by hyper-phosphorylated MED1. The effect of THZ1 phenocopies that for MED1 and CDK7 knockdown. SOURCE: Irfan Asangani (asangani@upenn.edu) - University of Pennsylvania