Intracrine Androgens and AKR1C3 Activation Confer Resistance to Enzalutamide in Prostate Cancer.

ABSTRACT: The introduction of enzalutamide and abiraterone has led to improvement in the treatment of metastatic castration-resistant prostate cancer. However, acquired resistance to enzalutamide and abiraterone therapies frequently develops within a short period in many patients. In the present study, we developed enzalutamide-resistant prostate cancer cells in an effort to understand the mechanisms of resistance. Global gene-expression analysis showed that the steroid biosynthesis pathway is activated in enzalutamide-resistant prostate cancer cells. One of the crucial steroidogenic enzymes, AKR1C3, was significantly elevated in enzalutamide-resistant cells. In addition, AKR1C3 is highly expressed in metastatic and recurrent prostate cancer and in enzalutamide-resistant prostate xenograft tumors. L

SUBMITTER: Liu C 

PROVIDER: S-EPMC4383695 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature