Franzén P, Ichijo H, Miyazono K
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Exp Cell Res. 1993 Jul;207(1):1-7. doi: 10.1006/excr.1993.1156.
The effects of transforming growth factor-beta 1 (TGF-beta 1) on a human prostatic carcinoma cell line PC-3, and its subclone PC-3U, were investigated. Dose-dependent inhibition of [3H]thymidine incorporation in PC-3U cells was observed by addition of TGF-beta 1, although only 50% inhibition was obtained by high concentrations (12 nM) of TGF-beta 1. The growth inhibitory effects of TGF-beta 1 on PC-3 cells was insignificant. When 0.3 ng/ml of phorbol 12-myristate 13-acetate (PMA) was added together with TGF-beta 1, TGF-beta 1 inhibited growth of PC-3 cells (about 50% inhibition), and the growth inhibitory activity of TGF-beta 1 in PC-3U cells was enhanced (more than 90% inhibition). Affinity crosslinking studies revealed that both cell lines possess all of the three described forms of TGF-beta receptors. The intensities of the crosslinked bands were weaker in the PC-3 cells than in PC-3U cells, and those were not increased by the addition of PMA. The expression of the TGF-beta type II receptor mRNA did not change after the addition of PMA or TGF-beta 1. These results suggest that the effects of PMA involved downstream components of the signal transduction pathway of TGF-beta 1. TGF-beta 1 is known to stimulate the production of extracellular matrix proteins and to induce changes in the expression of nuclear transcription factor genes. In both PC-3 and PC-3U cells, TGF-beta 1 was found to stimulate the induction of fibronectin and plasminogen activator inhibitor-1 and the expression of junB mRNA, and PMA did not affect these responses. Thus, PC-3 and PC-3U cells, which are partially resistant to the growth inhibitory activity of TGF-beta 1, could still respond to TGF-beta 1 by extracellular matrix production, independent of PMA action. These results suggest that different signalling pathways mediate TGF-beta 1-induced growth inhibition and stimulation of extracellular matrix accumulation in these cells.
研究了转化生长因子β1（TGF-β1）对人前列腺癌细胞系PC-3及其亚克隆PC-3U的影响。通过添加TGF-β1观察到PC-3U细胞中[3H]胸苷掺入的剂量依赖性抑制，尽管高浓度（12 nM）的TGF-β1仅获得50%的抑制。TGF-β1对PC-3细胞的生长抑制作用不显著。当0.3 ng/ml佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）与TGF-β1一起添加时，TGF-β1抑制PC-3细胞的生长（约50%抑制），并且TGF-β1在PC-3U细胞中的生长抑制活性增强（超过90%抑制）。亲和交联研究表明，两种细胞系都具有所描述的三种形式的TGF-β受体。PC-3细胞中交联带的强度比PC-3U细胞中的弱，并且添加PMA后强度没有增加。添加PMA或TGF-β1后，TGF-βII型受体mRNA的表达没有变化。这些结果表明，PMA的作用涉及TGF-β1信号转导途径的下游成分。已知TGF-β1刺激细胞外基质蛋白的产生并诱导核转录因子基因表达的变化。在PC-3和PC-3U细胞中，发现TGF-β1刺激纤连蛋白和纤溶酶原激活物抑制剂-1的诱导以及junB mRNA的表达，而PMA不影响这些反应。因此，对TGF-β1的生长抑制活性部分耐药的PC-3和PC-3U细胞仍可通过细胞外基质产生对TGF-β1作出反应，与PMA的作用无关。这些结果表明，不同的信号通路介导TGF-β1诱导这些细胞的生长抑制和细胞外基质积累的刺激。
