The p14ARF tumor suppressor restrains androgen receptor activity and prevents apoptosis in prostate cancer cells.

ABSTRACT: Prostate cancer (PCa) is characterized by a unique dependence on optimal androgen receptor (AR) activity where physiological androgen concentrations induce proliferation but castrate and supraphysiological levels suppress growth. This feature has been exploited in bipolar androgen therapy (BAT) for castrate resistant malignancies. Here, we investigated the role of the tumor suppressor protein p14ARF in maintaining optimal AR activity and the function of the AR itself in regulating p14ARF levels. We used a tumor tissue array of differing stages and grades to define the relationships between these components and identified a strong positive correlation between p14ARF and AR expression. Mechanistic studies utilizing CWR22 xenograft and cell culture models revealed that a decrease in AR reduce

SUBMITTER: Siddiqui S 

PROVIDER: S-EPMC8034238 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature