Remnant lipoproteins stimulate proliferation and activate MAPK and Akt signaling pathways via G protein-coupled receptor in PC-3 prostate cancer cells
Remnant lipoproteins stimulate proliferation and activate MAPK and Akt signaling pathways via G protein-coupled receptor in PC-3 prostate cancer cells
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DOI：
10.1016/j.cca.2007.04.016
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发表时间：
2007-08-01
影响因子：
5
通讯作者：
Suzuki, Kazuhiro
中科院分区：
文献类型：
--
作者：
Sekine, Yoshitaka;Koike, Hidekazu;Suzuki, Kazuhiro
背景：高甘油三酯血症最近被证明是前列腺癌的一个危险因素；然而，关于前列腺癌与富含甘油三酯的脂蛋白之间关系的报道很少。残馀脂蛋白（RLP）是一种富含tg的脂蛋白，由极低密度脂蛋白和乳糜微粒水解产生。我们研究了RLP对前列腺癌细胞增殖和信号转导的直接影响。方法：用抗apoa -1和抗apob -100的免疫亲和混合凝胶从人血清中分离RLP。采用NITS法对rlp诱导的细胞增殖进行评价。此外，我们通过Western blotting检测了RLP对MAPK和Akt信号转导的直接影响，这些信号转导被报道与前列腺癌相关。结果：RLP作用48 h后，前列腺癌PC-3细胞的增殖明显高于前列腺癌LNCaP细胞和人前列腺基质细胞。在PC-3细胞中，RLP还通过G蛋白偶联受体-蛋白激酶C依赖途径诱导MEK/ERK磷酸化。此外，RLP处理PC-3后，Akt通路被激活。结论：提示高甘油三酯血症，特别是残余高脂蛋白血症可能是前列腺癌的进展性因素之一。(C) 2007 Elsevier B.V.版权所有
Background: Hypertriglyceridemia was recently shown to be a risk factor for prostate cancer; however, there are only a few reports about the relationship between Prostate cancer and TG (triglycerides) rich lipoproteins. Remnant lipoproteins (RLP) are TG-rich lipoproteins, which are produced by the hydrolysis of very low density lipoproteins and chylomicrons. We examined the direct effect of RLP on the proliferation and signal transduction of prostate cancer cells.Methods: RLP were isolated from human serum with an immunoaffinity mixed gel containing anti-apoA-1 and anti-apoB-100. We evaluated RLP-induced cell proliferation by using NITS assay. Moreover we examined the direct effect of RLP on the MAPK and Akt signal transductions which are reported to be correlated with prostate cancer by using Western blotting.Results: Incubation in the presence of RLP for 48 h induced the proliferation of prostate cancer PC-3 cells more significantly than prostate cancer LNCaP cells and human prostate stromal cells. In PC-3 cells, RLP also induced the phosphorylation of MEK/ERK via a G protein-coupled receptor-protein kinase C dependent pathway. Moreover, activation of Akt pathway was observed after RLP treatment of PC-3.Conclusion: These findings suggested that hypertriglyceridemia, especially remnant hyperlipoproteinemia, might be one of the progressive factors for prostate cancer. (C) 2007 Elsevier B.V. All rights reserved.