Androgen receptor roles in benign and malignant prostate disease

Abstract

Androgen deprivation therapy (ADT), which aims to reduce androgen-androgen receptor (AR) signaling, is the normal method of prostate cancer treatment. Despite its early success in suppressing prostate tumor growth, the therapy eventually fails, leading to recurrent hormone-refractory tumor growth. Recent studies have been carried out with stromal cell-specific or fibroblast-specific AR knockout mice or prostate stromal-specific and epithelial-specific AR knockout transgenic mice prostate cancer models and in vitro and in vivo studies of various human prostate cancer cells with knock-in and knock-out of the AR. These have indicated that the AR in prostatic stroma acts as a proliferation stimulator and survival factor, whereas epithelial AR acts as a survival factor for epithelial luminal cells and stromal smooth muscle cell differentiation, and as a suppressor for epithelial basal intermediate cell proliferation. These two opposite roles of the stromal and epithelial AR pose a major challenge for ADT and should be taken into account when developing new therapies targeting AR in selective cells.