Signal Transduction Responses to Lysophosphatidic Acid and Sphingosine 1-Phosphate in Human Prostate Cancer Cells
Signal Transduction Responses to Lysophosphatidic Acid and Sphingosine 1-Phosphate in Human Prostate Cancer Cells
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DOI：
10.1002/pros.20994
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发表时间：
2009-10-01
期刊：
影响因子：
2.8
通讯作者：
Meier, Kathryn E.
中科院分区：
文献类型：
--
作者：
Gibbs, Terra C.;Rubio, Maria V.;Meier, Kathryn E.
背景资料。溶血磷脂酸(LPA)和鞘氨醇-1-磷酸(S1P)是与G蛋白偶联受体结合的脂质介质。在这项研究中，平行检测了三种人前列腺癌PC-3、Du145和LNCaP细胞对18：1 LPA和S1P的信号反应。方法用RT-PCR、Northern印迹和免疫印迹法检测受体的表达。结果所有细胞株均表达LPA和S1P受体的mRNA。PC-3和Du145在LPA和S1P刺激下增殖，而不是LNCaP。表皮生长因子(EGF)、佛波酯(PMA)、LPA和S1P可诱导PC-3和Du145中ERKs的激活，只有EGF和PMA能激活LNCaP中的ERKs。在Du145和PC-3中，Akt被EGF、LPA和S1P激活。AKT在LNCaP中具有结构性活性；EGF而不是LPA或S1P刺激进一步的磷酸化。在PC-3和Du145中，FAK同时被LPA和S1P磷酸化，但在LNCaP中不被磷酸化。LPA和S1P对不同细胞系的磷脂酶D(PLD)活性有不同程度的刺激作用。值得注意的是，这两种脂质介质都激活了LNCaP中的PLD。在Du145中，LPA而不是S1P激活PLD并增加细胞产生LPA。结论虽然LPA和S1P都能在所有研究的前列腺癌细胞系中诱导信号转导，但只有当ERK、Akt和FAK通路被激活时，才能观察到增殖反应。对脂质介质的其他反应，如PLD激活，可能有助于其他细胞结果。前列腺69：1493-1506,2009。(C)2009年Wiley-Liss，Inc.
BACKGROUND. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lipid mediators that bind to G-protein-coupled receptors. In this study, signaling responses to 18:1 LPA and S1P were examined in parallel in three human prostate cancer cell lines: PC-3, Du145, and LNCaP.METHODS. Receptor expression was assessed by RT-PCR, Northern blotting, and immunoblotting. Cellular responses to mediators were studied by proliferation assays, phosphoprotein immunoblotting, and phospholipid metabolism assays.RESULTS. All cell lines express mRNA for both LPA and S1P receptors. PC-3 and Du145, but not LNCaP, proliferate in response to LPA and S1P. Epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA), LPA, and S1P induce activation of Erks in PC-3 and Du145; only EGF and PMA activate Erks in LNCaP. In Du145 and PC-3, Akt is activated by EGF, LPA, and S1P. Akt is constitutively active in LNCaP; EGF but not LPA or S1P stimulates further phosphorylation. FAK is phosphorylated in response to both LPA and S1P in PC-3 and Du145, but not in LNCaP. LPA and S1P stimulate phospholipase D (PLD) activity to varying extents in the different cell lines. Notably, both lipid mediators activate PLD in LNCaP. In Du145, LPA, but not S1P, activates PLD and enhances cellular production of LPA.CONCLUSIONS. Although both LPA and S1P induce signal transduction in all prostate cancer cell lines studied, a proliferation response is observed only when the Erk, Akt, and FAK pathways are activated. Other responses to the lipid mediators, such as PLD activation, likely contribute to other cellular outcomes. Prostate 69: 1493-1506, 2009. (C) 2009 Wiley-Liss, Inc.