Schuurmans A L, Bolt J, Veldscholte J, Mulder E
Department of Endocrinology and Reproduction, Erasmus University Rotterdam, The Netherlands.
J Steroid Biochem Mol Biol. 1991;40(1-3):193-7. doi: 10.1016/0960-0760(91)90182-5.
The mitogenic activity of several growth factors on androgen responsive LNCaP human prostate tumor cells was studied. A two-fold stimulation of cell proliferation was observed after a culture period of 6 days in 1 ng EGF/ml, 10 ng TGF-alpha/ml or 20 ng basic FGF/ml. TGF-beta (0.02 ng/ml), which did not affect cell proliferation when added alone to the culture medium, inhibited the EGF- and TGF-alpha-induced growth. The synthetic androgen R1881 (0.1 nM) stimulated cell proliferation three-fold and increased the number of EGF receptors from 11500 to 28500 sites/cell. One of the mechanisms involved in androgen action on these cells is therefore an increased EGF receptor expression and increased sensitivity to EGF. TGF-beta did not directly affect androgen-responsive growth but inhibited the synergistic effect of EGF. A considerable expression of TGF alpha (precursors) could be demonstrated on the cells by immunohistochemical staining. However the staining intensity was not affected by androgens. These results make it less likely that androgen-responsive growth is mediated by regulation of secretion of an EGF- or TGF alpha-like activity, which in turn acts in an autocrine manner to stimulate growth. Estrogens, progestagens and antiandrogens do not inhibit androgen responsive growth of LNCaP cells but have striking growth stimulatory effects, increase EGF receptor level and increase acid phosphatase secretion. LNCaP cells contain a modified androgen receptor system with respect to both steroid specificity and antiandrogen sensitivity. It has recently been shown that the stimulatory effects are due to a mutated amino acid in the steroid binding domain of the androgen receptor.
研究了几种生长因子对雄激素反应性LNCaP人前列腺肿瘤细胞的促有丝分裂活性。在含有1 ng EGF/ml、10 ng TGF-α/ml或20 ng碱性FGF/ml的培养基中培养6天后，观察到细胞增殖有两倍的刺激作用。单独添加到培养基中时不影响细胞增殖的TGF-β（0.02 ng/ml）抑制了EGF和TGF-α诱导的生长。合成雄激素R1881（0.1 nM）刺激细胞增殖三倍，并使EGF受体数量从11500个/细胞增加到28500个/细胞。因此，雄激素对这些细胞作用的机制之一是EGF受体表达增加以及对EGF的敏感性增加。TGF-β不直接影响雄激素反应性生长，但抑制了EGF的协同作用。通过免疫组织化学染色可证明细胞上有相当量的TGFα（前体）表达。然而，染色强度不受雄激素影响。这些结果使得雄激素反应性生长由EGF或TGFα样活性分泌的调节介导的可能性降低，而这种调节反过来以自分泌方式刺激生长。雌激素、孕激素和抗雄激素不抑制LNCaP细胞的雄激素反应性生长，但具有显著的生长刺激作用，增加EGF受体水平并增加酸性磷酸酶分泌。LNCaP细胞在类固醇特异性和抗雄激素敏感性方面都含有一个修饰的雄激素受体系统。最近已表明，刺激作用是由于雄激素受体类固醇结合域中的一个氨基酸发生突变。
