Androgen receptor localisation and turnover in human prostate epithelium treated with the antiandrogen, Casodex

In vitro models of normal and malignant human prostate are currently limite d to a few well established cell lines that, with a single exception (LNCaP ), fail to express the androgen receptor (AR) - a common characteristic of prostatic epithelium grown in culture. To investigate the molecular mechani sm of action of the non-steroidal antiandrogen Casodex (bicalutamide) again st wild-type AR, we have established a transient AR expression model in non -tumorigenic prostate cells of both epithelial and mesenchymal origin. In t his model, both dihydrotestosterone and Casodex can effectively transport t he AR protein into the nucleus of prostate cells. Whereas the natural ligan d, dihydrotestosterone, stabilises the receptor, the AR is rapidly degraded at a nuclear location when the transfected cells are treated with Casodex. In contrast, whereas the mutant AR in the LNCaP line is also degraded on C asodex treatment over the same time period, its intracellular targeting is defective.