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Protease-activated receptor-2 regulates vascular endothelial growth factor expression in MDA-MB-231 cells via MAPK

Yingmei Liu1, Barbara M Mueller

  • 1Cancer Biology Division, La Jolla Institute for Molecular Medicine, San Diego, CA, USA.

Biochemical and Biophysical Research Communications
|May 3, 2006
PubMed

Insights

Protease-activated receptor 2 (PAR2) activation in breast cancer cells boosts vascular endothelial growth factor (VEGF) production via MAPK pathways. This suggests PAR2 signaling promotes angiogenesis in cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Protease-activated receptor 2 (PAR2) is a G-protein coupled receptor implicated in angiogenesis.
  • The precise mechanisms by which PAR2 influences angiogenesis, particularly in cancer, remain unclear.

Purpose of the Study:

  • To investigate the role of PAR2 activation in regulating vascular endothelial growth factor (VEGF) production in human breast cancer cells.
  • To elucidate the signaling pathways involved in PAR2-mediated VEGF upregulation.

Main Methods:

  • Human breast cancer cells were treated with various PAR2 agonists (peptide, trypsin, FVIIa) and other receptor activators.
  • VEGF mRNA and protein levels were quantified.
  • Cleavage blocking antibodies were used to confirm PAR2 mediation.
  • Mitogen-activated protein kinase (MAPK) pathway inhibitors (U0126, SB203580) were employed.
  • MAPK pathway activation (ERK1/2, p38) was assessed via phosphorylation assays.

Main Results:

  • PAR2 activation robustly increased VEGF message and protein in breast cancer cells.
  • Factor VIIa-mediated VEGF production was confirmed to be PAR2-dependent.
  • MAPK pathway inhibitors significantly blocked PAR2-mediated VEGF production.
  • PAR2 activation led to increased phosphorylation and activation of ERK1/2 and p38 MAPK.

Conclusions:

  • PAR2 signaling in breast cancer cells stimulates the production of the proangiogenic factor VEGF.
  • The MAPK signaling pathway (ERK1/2 and p38) is crucial for PAR2-mediated VEGF production.
  • These findings highlight PAR2 as a potential therapeutic target for modulating angiogenesis in breast cancer.

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