Farnesol induces thyroid hormone receptor (THR) β1 but inhibits THR-mediated signaling in MCF-7 human breast cancer cells
Farnesol induces thyroid hormone receptor (THR) β1 but inhibits THR-mediated signaling in MCF-7 human breast cancer cells
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DOI：
10.1016/j.bbrc.2006.02.145
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发表时间：
2006-04-28
影响因子：
3.1
通讯作者：
Archer, MC
中科院分区：
文献类型：
--
作者：
Duncan, RE;Archer, MC
法尼醇的抗癌作用已经得到了很好的证实，尽管调节这些作用的机制还不完全清楚。由于法尼醇已被证明通过激活法尼醇X受体和过氧化物酶体增殖物激活受体-α和-γ来调节基因转录，我们推测法尼醇也可能通过其他核激素受体来调节其部分作用。在这里，我们展示了在MCF-7人乳腺癌细胞中，法尼醇在抑制细胞生长的浓度下诱导甲状腺激素受体(Thr)(β1)mRNA和蛋白的表达。然而，Thr反应基因表达的变化表明法尼醇抑制Thr介导的信号转导。蛋白提取物泡沫细胞经法尼醇处理后，尽管Thrβ1含量较高，但与含有Thr反应元件共同序列的寡核苷酸的结合减少，这为解释细胞Thr转录活性降低提供了机制。(C)2006，Elsevier Inc.保留所有权利。
Anti-cancer effects of farnesol are well established, although mechanisms mediating these effects are not fully understood. Since farnesol has been shown to regulate gene transcription through activation of the farnesoid X receptor and the peroxisome proliferator-activated receptors-alpha and -gamma, we hypothesized that farnesol may also mediate some of its effects through other nuclear hormone receptors. Here we showed that in MCF-7 human breast cancer cells, farnesol induced the expression of thyroid hormone receptor (THR) (beta 1) mRNA and protein at concentrations that inhibited cell growth. Changes in the expression of THR responsive genes, however, suggested that farnesol inhibits THR-mediated signaling. Protein extracts froth cells treated with farnesol displayed decreased binding to oligode-oxynucleotides containing a consensus sequence for the THR response element, despite the higher THR beta 1 content, providing a mechanism to explain the decreased transcriptional activity of cellular THRs. (c) 2006, Elsevier Inc. All rights reserved.