期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 486, 期 1, 页码 58-63出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2009.03.010
关键词
CaR; EGR receptor; Metalloproteinases; TRPC1; Transactivation; Cell proliferation
The calcium sensing receptor (CaR) is a G-protein-coupled receptor that is activated by extracellular calcium ([Ca2+](o)). In MCF-7 human breast cancer cells, we previously reported that treatment with [Ca2+](o) for 24 h 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 [Ca2+](o) and EGF phosphorylate ERK1/2. Furthermore, inhibition of EGFR kinase and matrix metalloproteinases (MMPs) reduced the overall effects mediated by [Ca2+](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 [Ca2+](o) in MCF-7 cells. (C) 2009 Elsevier Inc. All rights reserved.
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