INHIBITION OF GROWTH AND INCREASE OF ACID-PHOSPHATASE BY TESTOSTERONEON ANDROGEN-INDEPENDENT MURINE PROSTATIC-CANCER CELLS TRANSFECTED WITH ANDROGEN RECEPTOR CDNA

Most androgen-unresponsive prostatic cancer cells are found to lack an drogen receptor (AR). To clarify the role of AR in the process of the progression from androgen-dependent to androgen-unresponsive tumor, th e AR gene was transfected into an AR-negative rat prostatic cancer cel l line CUB-II. AR-transfectant cells expressed AR mRNA and showed bind ing to R1881. AR was found in nuclei of AR-transfectant cells by histo chemical examination. Therefore, AR-transfectant cells were considered to contain functional AR. The growth of AR-transfectant cells was mar kedly inhibited in culture in the presence of testosterone, and the ef fect 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-tran sfectant cells in mice consisted of slightly larger spindle-shaped cel ls when compared to those of CUB-II cells. Moreover, AR-transfectant c ells contained a few polynuclear giant cells. Since CUB-II cells conta ined acid phosphatase (AcP) activity, the addition of testosterone in culture increased AcP activity of AR-transfectant cells. It is conclud ed that resumption of androgen-dependent processes reduces the growth rate accompanying changes of phenotype. (C) 1994 Wiley-Liss, Inc.