Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium
Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium
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DOI：
10.1016/j.taap.2007.12.017
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发表时间：
2008-05-01
影响因子：
3.8
通讯作者：
Shaikh, Zahir A.
中科院分区：
文献类型：
--
作者：
Liu, Zhiwei;Yu, Xinyuan;Shaikh, Zahir A.
镉（Cd）是一种内分泌干扰物，可诱导多种信号转导事件，包括ERK 1/2和AKT的激活。在这项研究中，雌激素受体（ER）在这些事件中的参与进行了评估，在三个人乳腺癌细胞系，MCF-7，MDA-MB-231，SK-BR-3。镉诱导的信号激活模式在三个细胞系模仿那些表现出响应于17 β-雌二醇。具体地说，表达ER α、ER β和GPR 30的MCF-7细胞用0.5-10 μ M Cd处理仅2.5分钟，就导致ERK 1/2的瞬时磷酸化。镉也引发了逐渐增加和持续激活AKT在60分钟的治疗期间。在只表达GPR 30的SK-BR-3细胞中，Cd也引起ERK 1/2的瞬时激活，但不引起AKT的瞬时激活。相比之下，在MDA-MB-231细胞中，仅表达ER β，镉不能引起ERK 1/2或AKT的快速激活。在MCF-7细胞中，在2.5分钟内的镉暴露也观察到ER α的瞬时磷酸化。虽然雌激素受体拮抗剂ICI 182，780不能阻止Cd对这些信号的影响，但针对hER α的特异性siRNA显著降低了Cd诱导的ERK 1/2活化，并完全阻断了AKT的活化。它的结论是，镉，雌二醇一样，可以引起ERK 1/2和AKT的快速激活，这些信号事件介导的可能的相互作用与膜ER α和GPR 30，但不是ER β。(c)2007年爱思唯尔公司All rights reserved.
Cadmium (Cd), an endocrine disruptor, can induce a variety of signaling events including the activation of ERK1/2 and AKT. In this study, the involvement of estrogen receptors (ER) in these events was evaluated in three human breast caner cell lines, MCF-7, MDA-MB-231, and SK-BR-3. The Cd-induced signal activation patterns in the three cell lines mimicked those exhibited in response to 17 beta-estradiol. Specifically, treatment of MCF-7 cells, that express ER alpha, ER beta and GPR30, to 0.5-10 mu M Cd for only 2.5 min resulted in transient phosphorylation of ERK1/2. Cd also triggered a gradual increase and sustained activation of AKT during the 60 min treatment period. In SK-BR-3 cells, that express only GPR30, Cd also caused a transient activation of ERK1/2, but not of AKT. In contrast, in MDA-MB-231 cells, that express only ER beta, Cd was unable to cause rapid activation of either ERK1/2 or AKT. A transient phosphorylation of ERa was also observed within 2.5 min of Cd exposure in the MCF-7 cells. While the estrogen receptor antagonist, ICI 182,780, did not prevent the effect of Cd on these signals, specific siRNA against hER alpha significantly reduced Cd-induced activation of ERK1/2 and completely blocked the activation of AKT. It is concluded that Cd, like estradiol, can cause rapid activation of ERK1/2 and AKT and that these signaling events are mediated by possible interaction with membrane ER alpha and GPR30, but not ER beta. (c) 2007 Elsevier Inc. All rights reserved.