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 differentiation of normal prostate epithelia, as well as the initial growth of prostate cancer cells. Nevertheless, prostate carcinomas eventually become androgen-unresponsive, and the cancer is refractory to hormonal therapy. To gain insight into the mechanism involved in this hormone-refractory phenomenon, we have examined the potential role of the androgen receptor (AR) in that process. We have investigated the expression of 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 cells. Our results are as follows. (i) Clone 33 LNCaP cells express AR, PAcP, and PSA, and cell growth is stimulated by 5alpha-dihydrotestosterone (DHT). Stimulation of cell growth correlates with decreased cellular PAcP activity. (ii) In clone 81 LNCaP cells, the expression of PAcP decreases with a concurrent decrease in the degree of androgen stimulation of cell growth, whereas the expression of PSA mRNA level is up-regulated by DHT, as in clone 33 cells. Conversely, in PAcP cDNA-transfected clone 81 cells, an additional expression of cellular PAcP correlates with an increased stimulation by androgen, higher than the corresponding control cells. (iii) PC-3 cells express a low level of functional 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-transfected PC-3 sublines, the expression of exogenous cellular PAcP correlates with androgen stimulation. This androgen stimulation of cell growth concurs with an increased tyrosine phosphorylation of a phosphoprotein of 185 kDa. In summary, the data indicate that the expression of AR alone is not sufficient for androgen stimulation of cell growth. Furthermore, in AR-expressing prostate cancer cells, the expression of cellular PAcP correlates with androgen stimulation of cell proliferation.
Lin
M F
MF
Department of Biochemistry/Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Meng
T C
TC
Rao
P S
PS
Chang
C
C
Schonthal
A H
AH
Lin
F F
FF
D000135:Acid Phosphatase / Q000378:metabolism*; D000728:Androgens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000502:physiology*; D013739:Testosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology
D000728:Androgens; D012333:RNA, Messenger; D011944:Receptors, Androgen; D019000:Phosphotyrosine; D013739:Testosterone; D010749:Phosphoprotein Phosphatases; D000135:Acid Phosphatase; D017430:Prostate-Specific Antigen