DIFFERENT SIGNALS MEDIATE TRANSFORMING GROWTH FACTOR-BETA-1-INDUCED GROWTH-INHIBITION AND EXTRACELLULAR-MATRIX PRODUCTION IN PROSTATIC-CARCINOMA CELLS

被引:70
作者
FRANZEN, P [1 ]
ICHIJO, H [1 ]
MIYAZONO, K [1 ]
机构
[1] LUDWIG INST CANC RES,BOX 595 BIOMED CTR,S-75124 UPPSALA,SWEDEN
关键词
D O I
10.1006/excr.1993.1156
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The effects of transforming growth factor-β1 (TGF-β1) 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-β1, although only 50% inhibition was obtained by high concentrations (12 nM) of TGF-β1. The growth inhibitory effects of TGF-β1 on PC-3 cells was insignificant. When 0.3 ng/ml of phorbol 12-myristate 13-acetate (PMA) was added together with TGF-β1, TGF-β1 inhibited growth of PC-3 cells (about 50% inhibition), and the growth inhibitory activity of TGF-β1 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-β 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-β type II receptor mRNA did not change after the addition of PMA or TGF-β1. These results suggest that the effects of PMA involved downstream components of the signal transduction pathway of TGF-β1. TGF-β1 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-β1 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-β1, could still respond to TGF-β1 by extracellular matrix production, independent of PMA action. These results suggest that different signalling pathways mediate TGF-β1-induced growth inhibition and stimulation of extracellular matrix accumulation in these cells. © 1993 Academic Press, Inc.
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页码:1 / 7
页数:7
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