, Volume 137, Issue 11, pp 1587-1594
Date: 09 Sep 2011

PI3K/Akt and MAPK/ERK1/2 signaling pathways are involved in IGF-1-induced VEGF-C upregulation in breast cancer

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Abstract

Objective

To investigate the signaling pathways involved in insulin-like growth factor-1 (IGF-1)-induced vascular endothelial growth factor C (VEGF-C) up-regulation and lymphatic metastasis in MDA-MB-231 breast cancer cells.

Methods

MDA-MB-231 breast cancer cells were exposed to IGF-1 with various concentrations. The expression level of VEGF-C was assessed by real-time PCR and Western blot. Akt and ERK1/2 phosphorylation was detected by Western blot. Signaling transduction inhibitors, LY294002 and PD98059, were used to block PI3K/Akt and MAPK/ERK1/2 signaling pathways, respectively.

Results

IGF-1 increased the level of VEGF-C expression in a dose-dependent manner in MDA-MB-231 breast cancer cells. In addition, phosphorylation of Akt and ERK1/2 was enhanced by IGF-1. Remarkably, inhibition of Akt phosphorylation by LY294002 completely blocked the effects on IGF-1-induced VEGF-C up-regulation. Inhibition of ERK1/2 phosphorylation by PD98059 reduced IGF-1-induced VEGF-C expression.

Conclusion

This study identified that PI3K/Akt and MAPK/ERK1/2 signaling pathways were involved in IGF-1-induced VEGF-C up-regulation and suggested their important roles in lymphatic metastasis in breast cancer.