ERK 1,2 and p38 pathways are involved in the proliferative stimuli mediated by urokinase in osteoblastic SaOS-2 cell line
ERK 1,2 and p38 pathways are involved in the proliferative stimuli mediated by urokinase in osteoblastic SaOS-2 cell line
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DOI：
10.1002/jcb.1211
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发表时间：
2001-01-01
影响因子：
4
通讯作者：
Martínez, J
中科院分区：
文献类型：
--
作者：
Juretic, N;Santibáñez, JF;Martínez, J
起源于前列腺癌的骨转移产生成骨反应，在体外通过增加成骨细胞的增殖来表达。尿激酶样纤溶酶原激活物(u-PA)存在于由前列腺癌细胞作为细胞膜受体W-PAR的配基的介质中，已被确定为调节这种增殖反应的特异性因子。本研究旨在揭示u-PA激活成骨细胞增殖的细胞内途径，并评价细胞受体u-PAR在这一增殖现象中的作用。我们的结果表明，在体外，u-PA通过激活ERK1和2的MAPK通路和p38通路来刺激SAOS-2成骨细胞的增殖。这些结果与甲醇胺和p38的特异性抑制剂Pd 098059和Sb 203580抑制中间激活和细胞增殖的作用一致。我们还发现，当细胞与u-PAR的第二天然配体Vitronectin相连时，SAOS-2细胞的增殖反应增强，并且在u-PA存在的情况下培养SAOS-2细胞代表了对u-PAR表达的刺激。在此基础上，我们认为成骨细胞对前列腺源性u-PA刺激的反应是非常有效的，这包括利用两种不同的信号通路和刺激u-PA受体的表达。J.细胞。生物化学。83：92-98,2001。(C)2001年Wiley-Liss，Inc.
Bone metastases from prostate origin generate an osteoblastic reaction that is expressed in vitro by increased osteoblast proliferation. The urokinase-like plasminogen activator (u-PA) present in the media conditioned by tumoral prostatic cells acting as a ligand of the cellular membrane receptor W-PAR), has been identified as the specific factor that modulates this proliferative reaction. The present study represents an effort to unravel the intracellular pathway by which u-PA activates osteoblastic proliferation and to evaluate the role of cellular receptor u-PAR in this proliferative phenomenon. Our results show that in vitro u-PA stimulates proliferation of SaOS-2 osteoblastic cells by activating the MAP kinase route of ERK1 and 2 and the p38 pathway. These results are in accordance with the inhibition of intermediate activation and cell proliferation by PD 098059 and SB 203580, specific inhibitors of MEK and p38, respectively. We also show that SaOS-2 cells increase their proliferative response when cells are plated onto vitronectin, the second natural ligand of u-PAR, and that culturing SaOS-2 cells in the presence of u-PA represents a stimuli for u-PAR expression. On the basis of these, results we propose that osteoblastic cel Is respond to the prostate-derived u-PA stimuli in a very efficient manner that includes the utilization of two different signaling routes and the stimulation of the expression of the u-PA receptor. J. Cell. Biochem. 83: 92-98, 2001. (C) 2001 Wiley-Liss, Inc.