EXPRESSION OF HUMAN PROSTATIC ACID-PHOSPHATASE CORRELATES WITH ANDROGEN-STIMULATED CELL-PROLIFERATION IN PROSTATE-CANCER CELL-LINES

Androgen plays a critical role in regulating the growth and differenti ation of normal prostate epithelia, as well as the initial growth of p rostate cancer cells, Nevertheless, prostate carcinomas eventually bec ome androgen-unresponsive, and the cancer is refractory to hormonal th erapy, To gain insight into the mechanism involved in this hormone-ref ractory phenomenon, we have examined the potential role of the androge n receptor (AR) in that process, We have investigated the expression o f AR and two prostate-specific androgen-responsive antigens, prostatic acid phosphatase (PAcP) and prostate-specific antigen (PSA), for the functional activity of AR in LNCaP and PC-3 human prostate carcinoma c ells, Our results are as follows. (i) Clone 33 LNCaP cells express AR, PAcP, and PSA, and cell growth is stimulated by 5 alpha-dihydrotestos terone (DHT). Stimulation of cell growth correlates with decreased cel lular PAcP activity. (ii) In clone 81 LNCaP cells, the expression of P AcP decreases with a concurrent decrease in the degree of androgen sti mulation of cell growth, whereas the expression of PSA mRNA level is u p-regulated by DHT, as in clone 33 cells. Conversely, in PAcP cDNA-tra nsfected clone 81 cells, an additional expression of cellular PAcP cor relates with an increased stimulation by androgen, higher than the cor responding control cells, (iii) PC-3 cells express a low level of func tional AR with no detectable PAcP or PSA, and the growth of PC-3 cells is not affected by DHT treatment, Nevertheless, in two PAcP cDNA-tran sfected PC-3 sublines, the expression of exogenous cellular PAcP corre lates with androgen stimulation, This androgen stimulation of cell gro wth concurs with an increased tyrosine phosphorylation of a phosphopro tein of 185 kDa, In summary, the data indicate that the expression of AR alone is not sufficient for androgen stimulation of cell growth, Fu rthermore, in AR-expressing prostate cancer cells, the expression of c ellular PAcP correlates with androgen stimulation of cell proliferatio n.