Androgens are not a direct requirement for the proliferation of human prostatic epithelium in vitro

The androgen receptor pathway is known to be a key regulator of growth in the normal and pathological prostate. However, the precise mechanisms of this signaling pathway with respect to the different cellular compartments of the prostate remain largely unknown. We have used a primary culture system to grow human prostatic epithelial cells of normal, benign, tumor and metastatic origin, as well as immortalized human prostatic epithelial cell lines, to demonstrate the absence of a direct or indirect effect of androgens on cellular proliferation in vitro. In parallel to this observed androgen independence for growth, all cell systems lost significant expression of androgen receptor, prostate-specific antigen and prostatic acid phosphatase. Since the androgen receptor is expressed in the epithelium in situ, our results suggest that the androgen effect on epithelial cells may be one of prostatic differentiation rather than proliferation, and that the androgen receptor/growth factor pathway acts through mesenchymal-epithelial interactions.