Schuurmans A L, Bolt J, Veldscholte J, Mulder E
Department of Biochemistry, Erasmus University Rotterdam, The Netherlands.
J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):849-53. doi: 10.1016/0960-0760(90)90431-j.
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.
LNCaP细胞（源自人类前列腺的淋巴结癌）呈现雄激素反应性生长。孕激素、雌二醇和抗雄激素与雄激素竞争结合细胞内的雄激素受体，其竞争程度高于其他雄激素敏感系统。添加合成雄激素R1881（0.1 nM）后观察到最佳生长状态（6天细胞培养物的DNA含量比对照增加3 - 4倍）。甾体类和非甾体类抗雄激素均未抑制雄激素反应性生长。在醋酸环丙孕酮浓度为10 nM或RU 23908浓度为100 nM时，生长甚至被刺激到与添加雄激素后相当的程度。醋酸环丙孕酮和RU 23908还使细胞表面表达的表皮生长因子受体数量增加到与雄激素相当的水平。与雄激素一样，醋酸环丙孕酮、RU 23908或雌二醇刺激培养液中每个细胞分泌前列腺特异性酸性磷酸酶。总之，抗雄激素可能由于雄激素受体系统缺陷而对LNCaP细胞的增殖产生显著的刺激作用。讨论了前列腺癌细胞中雄激素受体特异性的类似变化可能使这些细胞在生长速度上具有优势，并可能有助于发展为激素非依赖性肿瘤。
