Activation of the calcium-sensing receptor by high calcium induced breast cancer cell proliferation and TRPC1 cation channel over-expression potentially through EGFR pathways

Arch Biochem Biophys. 2009 Jun 1;486(1):58-63. doi: 10.1016/j.abb.2009.03.010. Epub 2009 Mar 28.

Abstract

The calcium sensing receptor (CaR) is a G-protein-coupled receptor that is activated by extracellular calcium ([Ca(2+)](o)). In MCF-7 human breast cancer cells, we previously reported that treatment with [Ca(2+)](o) for 24h leads to an over-expression of the Transient Receptor Potential Canonical 1 (TRPC1) cation channel and cell proliferation. Both involve the extracellular signal-regulated Kinases 1 & 2 (ERK1/2). MCF-7 also expressed epidermal growth factor receptor (EGFR) which is involved in cell proliferation through ERK1/2. Therefore, we investigated the cross-talk between CaR and EGFR in mediating ERK1/2 phosphorylation, TRPC1 over-expression and cell proliferation. Our data show that both high [Ca(2+)](o) and EGF phosphorylate ERK1/2. Furthermore, inhibition of EGFR kinase and matrix metalloproteinases (MMPs) reduced the overall effects mediated by [Ca(2+)](o) such as activation of ERK1/2, expression of TRPC1 and cell proliferation. They indicate the important role of the CaR-EGFR-ERK axis in transmitting mitogenic signals generated by high [Ca(2+)](o) in MCF-7 cells.

MeSH terms

  • Base Sequence
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Calcium / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Primers / genetics
  • Dipeptides / pharmacology
  • Enzyme Activation / drug effects
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Female
  • Gene Expression / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Quinazolines
  • Receptors, Calcium-Sensing / metabolism*
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • Transcriptional Activation / drug effects
  • Tyrphostins / pharmacology

Substances

  • DNA Primers
  • Dipeptides
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Quinazolines
  • Receptors, Calcium-Sensing
  • TRPC Cation Channels
  • Tyrphostins
  • transient receptor potential cation channel, subfamily C, member 1
  • RTKI cpd
  • Epidermal Growth Factor
  • ErbB Receptors
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Calcium