Stimulatory effects of antiandrogens on LNCaP human prostate tumor cell growth, EGF-receptor level and acid phosphatase secretion.
LNCaP cells (derived from a lymph node carcinoma of the human prostate) show androgen responsive growth. Progestagens, estradiol and antiandrogens competed with androgens for binding to the androgen receptor in the cells to a higher extent than in other androgen-sensitive systems. Optimal growth (3-4 fold increase in DNA content of 6 day cell cultures vs controls) was observed after addition of the synthetic androgen R1881 (0.1 nM). Both steroidal and non-steroidal antiandrogens did not suppress the androgen responsive growth. At a concentration of 10 nM cyproterone acetate or 100 nM RU 23908, growth was even stimulated to an extent comparable to that observed after addition of androgen. Cyproterone acetate and RU 23908 also increased the number of epidermal growth factor receptors expressed at the cell surface to a comparable level as did the androgen. Like androgens, cyproterone acetate, RU 23908 or estradiol stimulated the secretion per cell of prostate specific acid phosphatase in the culture fluid. In conclusion, antiandrogens can exert striking stimulatory effects on the proliferation of LNCaP cells probably due to a defective androgen receptor system. It is discussed that comparable changes in the specificity of the androgen receptor in prostate cancer cells may give these cells an advantage in growth rate and may contribute to development of tumors characterized as hormone independent.
Schuurmans
A L
AL
Department of Biochemistry, Erasmus University Rotterdam, The Netherlands.
Bolt
J
J
Veldscholte
J
J
Mulder
E
E
D000135:Acid Phosphatase / Q000378:metabolism*; D000726:Androgen Antagonists / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003534:Cyproterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017373:Cyproterone Acetate; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D007093:Imidazoles; D048289:Imidazolidines; D017373:Cyproterone Acetate; D004958:Estradiol; C021277:nilutamide; D003534:Cyproterone; D066246:ErbB Receptors; D000135:Acid Phosphatase