Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses.

ABSTRACT: Expression of androgen receptor (AR) in prostate cancer (PCa) is heterogeneous but the functional significance of AR heterogeneity remains unclear. Screening ~200 castration-resistant PCa (CRPC) cores and whole-mount sections (from 89 patients) reveals 3 AR expression patterns: nuclear (nuc-AR), mixed nuclear/cytoplasmic (nuc/cyto-AR), and low/no expression (AR^-/lo). Xenograft modeling demonstrates that AR⁺ CRPC is enzalutamide-sensitive but AR^-/lo CRPC is resistant. Genome editing-derived AR⁺ and AR-knockout LNCaP cell clones exhibit distinct biological and tumorigenic properties and contrasting responses to enzalutamide. RNA-Seq and biochemical analyses, coupled with experimental combinatorial therapy, identify BCL-2 as a critical therapeutic t

SUBMITTER: Li Q 

PROVIDER: S-EPMC6127155 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature