Delayed activation of extracellular-signal-regulated kinase 1/2 is involved in genistein- and equol-induced cell proliferation and estrogen-receptor-α-mediated transcription in MCF-7 breast cancer cells
Delayed activation of extracellular-signal-regulated kinase 1/2 is involved in genistein- and equol-induced cell proliferation and estrogen-receptor-α-mediated transcription in MCF-7 breast cancer cells
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DOI：
10.1016/j.jnutbio.2009.01.016
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发表时间：
2010-05-01
影响因子：
5.6
通讯作者：
Li, Zhong
中科院分区：
文献类型：
--
作者：
Liu, Huaqing;Du, Juan;Li, Zhong
本研究的目的是确定细胞外信号调节激酶1/2（ERK 1/2）通路是否参与染料木素和雌马酚诱导的细胞增殖和雌激素受体（ER）的反式激活。对于MCF-7人乳腺细胞，低浓度的染料木黄酮和雌马酚增强增殖并诱导MCF-7细胞进入S期。雌马酚和金雀异黄素诱导的细胞增殖和S期进入被ER α拮抗剂4-羟基他莫昔芬和ICI 182，780和丝裂原活化蛋白激酶1/2抑制剂U 0126阻断。这些数据表明，ER α和丝裂原活化蛋白胞外激酶/ERK信号是染料木黄酮/雌马酚对细胞生长和细胞周期进程的影响所必需的。染料木黄酮和雌马酚诱导ERK 1/2激活延迟和延长。通过U 0126抑制ERK 1/2磷酸化导致完全抑制染料木素和雌马酚诱导的雌激素反应元件报告活性，并抑制雌激素反应基因pS2。抗雌激素ICI对染料木素和雌马酚诱导的ERK 1/2磷酸化没有影响。这些结果表明，ERK 1/2的激活位于ER介导的转录上游，并且ERK 1/2的激活对于ER α的反式激活是必需的。总之，染料木黄酮和雌马酚引起ERK 1/2的延迟激活，这种激活似乎参与乳腺癌细胞的增殖和雌激素依赖性转录激活。(C)2010年爱思唯尔公司All rights reserved.
The aim of this study was to determine whether the extracellular-signal-regulated kinase 1/2 (ERK1/2) pathway is involved in genistein- and equol-induced cell proliferation and estrogen receptor (ER) a transactivation. For MCF-7 human breast cells, low concentrations of genistein and equol enhanced proliferation and induced MCF-7 cells to enter the S-phase. Genistein- and equol-induced cell proliferation and S-phase entry were blocked by the ER alpha antagonists 4-hydroxytamoxifen and ICI 182,780 and by the mitogen-activated protein kinase 1/2 inhibitor U0126. These data indicated that ERa and mitogen-activated protein extracellular kinase/ERK signaling were required for the effects of genistein/equol on cell growth and cell cycle progression. Genistein and equol induced delayed and prolonged activation of ERK1/2. Inhibition of ERK1/2 phosphorylation by U0126 led to complete suppression of genistein- and equol-induced estrogen response element reporter activity and to suppression of the estrogen-responsive gene pS2. The anti-estrogen ICI had no effect on genistein- and equol-induced ERK1/2 phosphorylation. These results suggest that activation of ERK1/2 lies upstream of ER-mediated transcription, and that ERK1/2 activation is necessary for the transactivation of ERa. In conclusion, genistein and equol elicit a delayed activation of ERK1/2, and this activation appears to be involved in the proliferation of breast cancer cells and estrogen-dependent transcriptional activation. (C) 2010 Elsevier Inc. All rights reserved.