Different signalling pathways regulate VEGF and IL-8 expression in breast cancer: implications for therapy

被引:46
作者
Chelouche-Lev, D
Miller, CP
Tellez, C
Ruiz, M
Bar-Eli, M
Price, JE
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
[2] Univ Texas, Grad Sch Biomed Sci, Canc Biol Program, Houston, TX 77030 USA
关键词
angiogenic cytokines; breast cancer; mitogen-activated protein kinase; phosphatidylinositol-3-kinase;
D O I
10.1016/j.ejca.2004.05.024
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2509 / 2518
页数:10
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