Electromagnetic fields alter the expression of estrogen receptor cofactors in breast cancer cells
Electromagnetic fields alter the expression of estrogen receptor cofactors in breast cancer cells
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DOI：
10.1002/bem.20387
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发表时间：
2008-04-01
影响因子：
1.9
通讯作者：
Hanf, Volker
中科院分区：
文献类型：
--
作者：
Girgert, Rainer;Gruendker, Carsten;Hanf, Volker
乳腺癌是西方社会女性最常见的恶性肿瘤。越来越多的人暴露在电磁场中，这被怀疑是工业化国家乳腺癌发病率上升的原因之一。大多数乳腺肿瘤是用部分抗雌激素他莫昔芬治疗的。大多数肿瘤在治疗过程中对他莫昔芬产生抗药性，导致治疗失败。电磁场降低他莫昔芬的疗效，类似于他莫昔芬的耐药性。在本研究中，我们研究了电磁场影响三苯氧胺敏感性的机制。在暴露于1.2mU T 50赫兹电磁场的细胞中，比较了雌激素受体辅助因子的基因表达。利用基因阵列技术，发现了几个辅助因子的差异表达。RT-PCR检测SRC-I和AIB-1以及N-Cor和SMRT两种辅阻遏子的表达。两种辅活化子在暴露的细胞中表达更强，而两种辅抑制子的表达减少。通过Western blotts验证了RNA分析的正确性。电磁场对辅活化子和辅抑制子基因表达的反向改变导致对他莫昔芬的敏感性降低。电磁场可能在体内诱导他莫昔芬耐药。《生物电磁学》29：169-176,2008。(C)2007年Wiley-Liss，Inc.
Breast cancer is the most common malignancy of women in Western societies. The increasing exposure to electromagnetic fields has been suspected to contribute to the rising incidence of breast cancer in industrialized Countries. The majority of breast tumors is treated with the partial antiestrogen tamoxifen. Most tumors become resistant to tamoxifen in the course of treatment resulting in treatment failure. Electromagnetic fields reduce the efficacy of tamoxifen similar to tamoxifen resistance. In this study we investigated the mechanism by which electromagnetic fields influence the sensitivity to tamoxifen. In cells exposed to 1.2 mu T of a 50 Hz electromagnetic field gene expression of cofactors of the estrogen receptors was compared to sham exposed cells. Using a gene array technology several cofactors were found to be differentially expressed. The expression of the coactivators, SRC-I and AIB 1, and of two corepressors, N-Cor and SMRT, was quantified by RT-PCR. Both coactivators were expressed more strongly in the exposed cells while the expression of two corepressors decreased. The RNA analysis was confirmed by Western blots. The contradirectional changes in gene expression of coactivators and corepressors by electromagnetic fields results in a lower sensitivity to tamoxifen. Electromagnetic fields may contribute to the induction of tamoxifen resistance in vivo. Bioelectromagnetics 29:169-176, 2008. (C) 2007 Wiley-Liss, Inc.