Additive effects of EGF and IL-1ß regulate tumor cell migration and invasion in gastric adenocarcinoma via activation of ERK1/2.
Int J Oncol
; 45(1): 291-301, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24789460
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-1ß) to activate extracellular signal-regulated kinase (ERK)1/2 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-1ß and EGF plus IL-1ß 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-1ß additively activated ERK1/2, increased migration and invasion than either EGF or IL-1ß 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-1ß, EGF plus IL-1ß, 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-1ß/ERK1/2 pathways may be key pathways closely associated with GA progression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Adenocarcinoma
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Proteína Quinasa 1 Activada por Mitógenos
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Proteína Quinasa 3 Activada por Mitógenos
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Factor de Crecimiento Epidérmico
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Interleucina-1beta
/
Invasividad Neoplásica
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Grecia