Different signalling pathways regulate VEGF and IL-8 expression in breast cancer: implications for therapy
Different signalling pathways regulate VEGF and IL-8 expression in breast cancer: implications for therapy
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DOI：
10.1016/j.ejca.2004.05.024
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发表时间：
2004-11-01
影响因子：
8.4
通讯作者：
Price, JE
中科院分区：
文献类型：
--
作者：
Chelouche-Lev, D;Miller, CP;Price, JE
促血管生成细胞因子的表达升高与肿瘤的侵袭性生长和乳腺癌患者的生存率降低有关。一般来说，血管内皮生长因子（VEGF）高表达的乳腺癌细胞系也表达高水平的白细胞介素-8（IL-8）。在四种细胞系中检查了抑制丝裂原激活蛋白激酶 (MAPK) 和磷脂酰肌醇 3 激酶 (PI3K) 的结果，这两种酶都与这些细胞因子的调节有关。用丝裂原激活蛋白激酶/细胞外信号相关激酶 (MEK) 抑制剂 U0126 治疗可降低 MDA-MB-231 细胞中 VEGF 和 IL-8 的表达，部分抑制 MDA-MB-468 和 Hs578T 细胞中的表达，对 GI101A 细胞的影响最小。 LY294002 治疗可降低 GI101A 和 MDA-MB-468 细胞中的细胞因子表达，部分降低 Hs578T，对 MDA-MB-231 细胞影响较小。因此，IL-8和VEGF在不同细胞系中受到不同信号通路的调节；这表明抑制主要活性途径可以下调两种血管生成细胞因子。识别哪个信号通路处于活跃状态可以确定乳腺癌抗血管生成治疗的靶点。 (C) 2004 Elsevier Ltd. 保留所有权利。
Elevated expression of pro-angiogenic cytokines is associated with aggressive tumour growth and decreased survival of patients with breast cancer. In general, the breast cancer cell lines with high vascular endothelial growth factor (VEGF) expression also express high levels of interleukin-8 (IL-8). The consequence of inhibiting mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K), both implicated in regulation of these cytokines, was examined in four cell lines. Treatment with the mitogen-activated protein kinase/extracellular signal-related kinase (MEK) inhibitor U0126 reduced expression of VEGF and IL-8 in MDA-MB-231 cells, partially inhibited expression in MDA-MB-468 and Hs578T cells, with minimal effects in GI101A cells. Treatment with LY294002 reduced cytokine expression in GI101A and MDA-MB-468 cells, with partial reduction in Hs578T and less effect in MDA-MB-231 cells. Thus, IL-8 and VEGF were regulated by different signalling pathways in different cell lines; this suggests that inhibition of the dominantly active pathway can downregulate both angiogenic cytokines. Recognising which signalling pathway is active may identify targets for anti-angiogenic therapy of breast cancer. (C) 2004 Elsevier Ltd. All rights reserved.