Additive effects of EGF and IL-1 beta regulate tumor cell migration and invasion in gastric adenocarcinoma via activation of ERK1/2

作者：Han, Junyong; Xie, Yanchuan; Lan, Fenghua; Yu, Yinghao; Liu, Wei; Chen, Jinhua; Zheng, Feng; Ouyang, Xuenong; Lin, Xiangquan; Lin, Yanhong; Huang, Qiaojia^*; Wang, Lie; Tan, Jianming

来源：International Journal of Oncology, 2014, 45(1): 291-301.

DOI：10.3892/ijo.2014.2401

• epidermal growth factor and interleukin-1 beta
• additive effect
• extracellular signal-regulated kinase1/2
• gastric adenocarcinoma
• metastasis

Growth and inflammatory factors are associated with poor prognosis in gastric adenocarcinoma (GA); however, the additive effects of growth and inflammatory factors in GA remain unclear. In this study, we investigated the ability of epidermal growth factor (EGF) and interleukin (IL-1 beta) to activate extracellular signal-regulated kinase (ERK)112 in GA cells, and correlated the relationships between their roles with the metastatic potential both in GA cells and GA tissues. The effects of EGF, IL-1 beta and EGF plus IL-1 beta in AGS and MKN-45 GA cells were examined using western blotting, Transwell migration and invasion assays, immunocytochemical staining and an activator protein (AP)-1 luciferase reporter gene assay, and was further characterized in GA tissues by immunohistochemistry. The results exhibited that EGF and IL-1 beta additively activated ERK1/2, increased migration and invasion than either EGF or IL-1 beta alone in AGS and MKN-45 cells. The mechanisms were involved in upregulating MMP-9 expression through increasing AP-1 transcriptional activity via ERK1/2 pathway; these effects were dose-dependently inhibited by silencing ERK1/2 or using U0126. In vivo data also confirmed that the overexpression of p-ERK1/2 in GA tissues correlated well with the EGF, IL-1 beta, EGF plus IL-1 beta, and was associated with metastasis, which was well correlation with the expression of MMP-9 and c-fos (AP-1). The results demonstrate that growth and inflammatory factors play an important role in metastasis of GA by additively activating ERK-1/2 and AP-1, and upregulating MMP-9. As both cytokines contribute to the migration and invasion of GA cells, EGF/IL-1 beta/ERK1/2 pathways may be key pathways closely associated with GA progression.

• 出版日期2014-7
• 单位中国人民解放军南京军区福州总医院