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

  • Chenfang Zhu
  • Xiaoliang Qi
  • Yaning Chen
  • Bo Sun
  • Yalei Dai
  • Yan Gu
Review

DOI: 10.1007/s00432-011-1049-2

Cite this article as:
Zhu, C., Qi, X., Chen, Y. et al. J Cancer Res Clin Oncol (2011) 137: 1587. doi:10.1007/s00432-011-1049-2

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.

Keywords

Breast cancer IGF-1 VEGF-C Akt ERK1/2 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Chenfang Zhu
    • 1
  • Xiaoliang Qi
    • 1
  • Yaning Chen
    • 1
  • Bo Sun
    • 1
  • Yalei Dai
    • 2
  • Yan Gu
    • 1
  1. 1.Department of General SurgeryShanghai Ninth People’s Hospital, Affiliated to Shanghai Jiaotong University, School of MedicineShanghaiChina
  2. 2.Department of ImmunologyShanghai Tongji University, School of MedicineShanghaiChina

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