Inhibition of growth and increase of acid phosphatase by testosterone on androgen-independent murine prostatic cancer cells transfected with androgen receptor cDNA.

Abstract

Most androgen-unresponsive prostatic cancer cells are found to lack androgen receptor (AR). To clarify the role of AR in the process of the progression from androgen-dependent to androgen-unresponsive tumor, the AR gene was transfected into an AR-negative rat prostatic cancer cell line CUB-II. AR-transfectant cells expressed AR mRNA and showed binding to R1881. AR was found in nuclei of AR-transfectant cells by histochemical examination. Therefore, AR-transfectant cells were considered to contain functional AR. The growth of AR-transfectant cells was markedly inhibited in culture in the presence of testosterone, and the effect of testosterone was reduced by simultaneous addition of flutamide. Moreover, tumors inoculated with AR-transfectant cells in male mice showed much slower growth than those in females. The tumors of AR-transfectant cells in mice consisted of slightly larger spindle-shaped cells when compared to those of CUB-II cells. Moreover, AR-transfectant cells contained a few polynuclear giant cells. Since CUB-II cells contained acid phosphatase (AcP) activity, the addition of testosterone in culture increased AcP activity of AR-transfectant cells. It is concluded that resumption of androgen-dependent processes reduces the growth rate accompanying changes of phenotype.