Folic acid enforces DNA methylation-mediated transcriptional silencing of PTEN, APC and RARbeta2 tumour suppressor genes in breast cancer
Folic acid enforces DNA methylation-mediated transcriptional silencing of PTEN, APC and RARbeta2 tumour suppressor genes in breast cancer
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DOI：
10.1016/j.bbrc.2012.11.103
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发表时间：
2013-01-11
影响因子：
3.1
通讯作者：
Fabianowska-Majewska, Krystyna
中科院分区：
文献类型：
--
作者：
Lubecka-Pietruszewska, Katarzyna;Kaufman-Szymczyk, Agnieszka;Fabianowska-Majewska, Krystyna
叶酸是研究最多的饮食化合物之一，最近已成为食品强化辩论的主要话题。虽然低叶酸水平可能与癌症发展的风险增加有关，但同时一些报告表明，高叶酸浓度所介导的有害影响。采用甲基化敏感的限制性内切酶分析(MSRA)和实时荧光定量RT-PCR方法，检测了叶酸对不同侵袭能力的乳腺癌细胞株MCF-7和MDA-MB-231中DNA启动子甲基化及抑癌基因PTEN、APC和RARbeta2表达的影响。被测试的基因编码的蛋白质参与了致癌细胞内信号通路的调节。结果表明，随着叶酸浓度的增加，肿瘤抑制基因的表达呈剂量依赖性下调，这可能与其启动子区域的DNA甲基化增加有关。在非侵袭性的MCF-7细胞中效果更为显著，我们还观察到在最高叶酸浓度下DNMT1的表达上调了30%。我们的发现表明，在引入叶酸补充剂时需要谨慎，因为它可能会导致癌症进展。(C)2012 Elsevier Inc.保留所有权利。
Folate, one of the most studied dietary compounds, has recently become the main topic of debates on food fortification. Although low folate levels may be associated with increased risk of cancer development, simultaneously several reports indicate a detrimental effects mediated by high folate concentrations. Using the methylation sensitive restriction analysis (MSRA) and real-time RT-PCR we tested the effect of folic acid on DNA promoter methylation and expression of PTEN, APC and RARbeta2 tumour suppressor genes in MCF-7 and MDA-MB-231 breast cancer cell lines with different invasive capacity. The tested genes encode proteins involved in regulation of oncogenic intracellular signaling pathways. The results show that the increasing concentrations of folic acid lead to a dose-dependent down-regulation of tumour suppressor genes which may be linked to the increased DNA methylation detected within their promoter regions. The effects were more remarkable in non-invasive MCF-7 cells where we also observed 30% up-regulation of DNMT1 expression at the highest folate concentration used. Our findings show that caution need to be used when introducing folic acid supplementation since it may lead to cancer progression. (C) 2012 Elsevier Inc. All rights reserved.