S100A8 and S100A9 activate MAP kinase and NF-κB signaling pathways and trigger translocation of RAGE in human prostate cancer cells
S100A8 and S100A9 activate MAP kinase and NF-κB signaling pathways and trigger translocation of RAGE in human prostate cancer cells
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DOI：
10.1016/j.yexcr.2005.10.013
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发表时间：
2005-01-15
影响因子：
3.7
通讯作者：
Mayer, D
中科院分区：
文献类型：
--
作者：
Hermani, A;De Servi, B;Mayer, D
S100蛋白是一个多基因的钙结合蛋白家族，近年来被认为与人类的病理学有关。据报道，S100蛋白（包括S100 A8和S100 A9）的表达失调与肿瘤性疾病相关。在先前的研究中，我们鉴定了S100 A8和S100 A9在人前列腺癌中的增强表达。为了研究S100 A8和S100 A9在前列腺癌中的潜在功能意义，我们研究了过表达和纯化的重组S100 A8和S100 A9蛋白在不同前列腺上皮细胞系中的影响。S100 A8和S100 A9由前列腺癌细胞分泌，这一发现促使我们分析作为细胞外配体的可能功能。S100 A8/A9可诱导NF-κ B B的活化和p38和p44/42 MAP激酶磷酸化的增加。此外，细胞外S100 A8/A9刺激良性前列腺细胞在体外的迁移。此外，在免疫荧光实验中，我们发现在用重组S100 A8/A9蛋白刺激细胞或通过增加胞质Ca 2+水平刺激细胞后，细胞内S100 A8/A9与Ca 2+有强烈的斑点共定位。总之，我们的研究结果表明，S100 A8和S100 A9与前列腺癌细胞重要特征的激活有关。(c)2005年爱思唯尔公司All rights reserved.
S100 proteins, a multigenic family of calcium-binding proteins, have been linked to human pathologies in recent years. Deregulated expression of S100 proteins, including S100A8 and S100A9, was reported in association with neoplastic disorders. In a previous study, we identified enhanced expression of S100A8 and S100A9 in human prostate cancer. To investigate potential functional implications of S100A8 and S100A9 in prostate cancer, we examined the influence of over-expressed and of purified recombinant S100A8 and S100A9 proteins in different prostate epithelial cell lines. S100A8 and S100A9 were secreted by prostate cancer cells, a finding which prompted us to analyze a possible function as extracellular ligands. S100A8/A9 induced the activation of NF-kappa B and an increased phosphorylation of p38 and p44/42 MAP kinases. In addition, extracellular S100A8/A9 stimulated migration of benign prostatic cells in vitro. Furthermore, in immunofluorescence experiments, we found a strong speckled co-localization of intracellular Sl00A8/A9 with RAGE after stimulating cells with recombinant S100A8/A9 protein or by increasing cytosolic Ca2+ levels. In summary, our findings show that S100A8 and S100A9 are linked to the activation of important features of prostate cancer cells. (c) 2005 Elsevier Inc. All rights reserved.