Docosahexaenoic Acid Downregulates EGF-Induced Urokinase Plasminogen Activator and Matrix Metalloproteinase 9 Expression by Inactivating EGFR/ErbB2 Signaling in SK-BR3 Breast Cancer Cells.
Nutr Cancer
; 67(5): 771-82, 2015.
Article
en En
| MEDLINE
| ID: mdl-25970488
ABSTRACT
Urokinase plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) play crucial roles in tumor metastasis. Despite the well-known anticancer role of docosa-hexaenoic acid (DHA), its specific effect on ErbB2-mediated breast cancer metastasis is not fully clarified. In this study, we investigated the effect of DHA on epidermal growth factor (EGF)-induced uPA and MMP-9 activity, expression and cell invasion in SK-BR3 breast cancer cells and the possible mechanisms involved. The results showed that EGF (40 ng/ml) induced uPA and MMP-9 mRNA and protein expression, enzyme activity, and 100 µM DHA significantly inhibited EGF-induced uPA and MMP-9 mRNA, protein expression, enzyme activity, cell migration, and cell invasion. EGF increased protein expression and phosphorylation of EGF receptor (EGFR) and ErbB2 as well as of JNK2, ERK1/2, and Akt, and these changes were attenuated by DHA pretreatment. AG1478, an inhibitor of EGFR, also attenuated EGF-induced activation of EGFR, JNK2, ERK1/2, and Akt. Knocked down ErbB2 expression resulted in a similar inhibition of uPA and MMP-9 expression as noted by DHA and AG1478. Taken together, these results suggest that suppression of EGF-induced metastasis by DHA is likely through an inhibition of EGFR and ErbB2 protein expression and the downstream target uPA and MMP-9 activation in SK-BR3 human breast cancer cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Activador de Plasminógeno de Tipo Uroquinasa
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Ácidos Docosahexaenoicos
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Receptor ErbB-2
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Metaloproteinasa 9 de la Matriz
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Factor de Crecimiento Epidérmico
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Receptores ErbB
Límite:
Female
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Humans
Idioma:
En
Revista:
Nutr Cancer
Año:
2015
Tipo del documento:
Article
País de afiliación:
Taiwán