Activation of the calcium-sensing receptor by high calcium induced breast cancer cell proliferation and TRPC1 cation channel over-expression potentially through EGFR pathways
Activation of the calcium-sensing receptor by high calcium induced breast cancer cell proliferation and TRPC1 cation channel over-expression potentially through EGFR pathways
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DOI：
10.1016/j.abb.2009.03.010
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发表时间：
2009-06-01
影响因子：
3.9
通讯作者：
Ahidouch, Ahmed
中科院分区：
文献类型：
--
作者：
El Hiani, Yassine;Lehen'kyi, Vadil;Ahidouch, Ahmed
钙敏感受体（CaR）是一种G蛋白偶联受体，由细胞外钙（[Ca 2 +]（o））激活。在MCF-7人乳腺癌细胞中，我们先前报道了用[Ca 2 +]（o）处理24 h导致瞬时受体电位典型1（TRPC 1）阳离子通道的过表达和细胞增殖。两者都涉及细胞外信号调节激酶1和2（ERK 1/2）。MCF-7还表达表皮生长因子受体（EGFR），其通过ERK 1/2参与细胞增殖。因此，我们研究了CaR和EGFR在介导ERK 1/2磷酸化、TRPC 1过表达和细胞增殖中的相互作用。我们的数据表明，高[Ca 2 +]（o）和EGF都磷酸化ERK 1/2。此外，EGFR激酶和基质金属蛋白酶（MMP）的抑制降低了[Ca 2 +]（o）介导的总体效应。如ERK 1/2激活、TRPC 1表达和细胞增殖。这表明CaR-EGFR-ERK轴在MCF-7细胞中传递高[Ca 2 +]（o）产生的促有丝分裂信号中的重要作用。(C)2009 Elsevier Inc. All rights reserved.
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.