ERK1/2 and p38 pathways are required for P2Y receptor-mediated prostate cancer invasion
ERK1/2 and p38 pathways are required for P2Y receptor-mediated prostate cancer invasion
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DOI：
10.1016/j.canlet.2004.05.023
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发表时间：
2004-11-25
期刊：
影响因子：
9.7
通讯作者：
Fang, WG
中科院分区：
文献类型：
--
作者：
Chen, L;He, HY;Fang, WG
G蛋白偶联的P2 Y嘌呤受体具有广泛的生理功能，但其在肿瘤进展中的作用尚不清楚。在这里，我们报告说，P2 Y受体的刺激增强前列腺癌细胞侵袭在两个人前列腺癌细胞系，这是由ERK 1/2和p38信号通路介导的。P2 Y激动剂刺激前列腺癌细胞的侵袭，并增加ERK 1/2和p38蛋白激酶的活性。MEK 1抑制剂PD 98059或p38抑制剂SB 203580的存在抑制了刺激的癌细胞侵袭。MEK 1的显性负突变体（KA-MEK 1）的表达或MKP-5（p38的双特异性磷酸酶）的上调都降低了培养的前列腺癌细胞的侵袭。这些结果表明，P2 Y受体及其下游ERK 1/2和p38蛋白激酶是促进前列腺癌侵袭的重要调节因子。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
The G protein-coupled P2Y purinoceptors have wide physiological functions, but their role(s) in tumor progression remain unclear. Here, we report that stimulation of P2Y receptors enhances prostate cancer cell invasion in two human prostate carcinoma cell lines, which is mediated by ERK1/2 and p38 signaling pathways. P2Y agonists stimulated prostate cancer cell invasion, and increased the activities of ERK1/2 and p38 protein kinases. The stimulated cancer cell invasion was inhibited by the presence of MEK1 inhibitor PD98059 or p38 inhibitor SB203580. Expression of dominant-negative mutant of MEK1 (KA-MEK1), or up-regulation of MKP-5 (a dual-specificity phosphatase of p38), both reduced the invasion of cultured prostate cancer cells. These results suggest that P2Y receptors and their down-stream ERK1/2 and p38 protein kinases are important regulators promoting prostate cancer invasion. (C) 2004 Elsevier Ireland Ltd. All rights reserved.