Omics A Journal of Integrative Biology, 2012, 16(5):235-44.

Can Soy Phytoestrogens Decrease DNA Methylation in BRCA1 and BRCA2 Oncosuppressor Genes in Breast Cancer?

Rémy Bosviel, Elise Dumollard, Pierre Déchelotte, et al

Centre Jean Perrin, Département d'Oncogénétique, CBRV, Clermont-Ferrand, France

Although soy phytoestrogens have been postulated to exert a protective effect against breast cancer, the attendant mechanisms, in particular epigenetics underpinnings, have remained elusive. We investigated the putative effects on DNA methylation by two naturally occurring isoflavones, genistein and daidzein, in a study of the BRCA1 and BRCA2 oncosuppressor genes in breast cancer cell lines (MCF-7, MDA-MB 231, and MCF10a). A demethylant agent, the 5-azacytidine, and a methylant, the budesonide, were used as treatment controls. DNA methylation of BRCA1 and BRCA2 was investigated with methylated DNA immunoprecipitation coupled with PCR. In parallel, protein expression was determined by Western blot, immunohistochemistry, and confocal microscopy. Our results suggest that treatment with 18.5 μM Genistein or 78.5 μM Daidzein might reverse DNA hypermethylation and restore the expression of the oncosuppressor genes BRCA1 and BRCA2. 5-Azacitydine also enhanced the reexpression of these genes while budesonide had an opposite effect. To the best of our knowledge, these observations, while requiring replication, provide new evidence on potential epigenetic mechanisms by which genistein and daidzein might contribute to regulation of the BRCA1 and BRCA2. Future studies are warranted on whether the demethylating effect of genistein and daidzein is global or focused on select candidate genes.

美国《综合生物学基因组学A杂志》，2012年5月

在乳腺癌中大豆植物雌激素可以减少BRCA1 和 BRCA2 双抑制基因中的DNA 甲基化吗？

雷米 博斯维埃尔，艾丽萨 达姆劳德，皮埃尔 德科洛特，等

法国克莱蒙费朗让 佩林中心遗传部

虽然大豆植物雌激素能预防乳腺癌发挥保护作用，但其相应的机制，特别是表观遗传学机理仍难以捉摸。我们使用两种天然异黄酮，金雀异黄素和大豆黄酮，在乳腺癌细胞（MCF-7、 MDA-MB 231 和 MCF10a） 中的BRCA1 和 BRCA2 抑制肿瘤基因的研究中探究其对 DNA 甲基化的假设影响。一种去甲基化试剂，5-氮杂胞苷和甲基化试剂，布地奈德，被用作对照治疗。用甲基化 DNA 免疫共沉淀和聚合酶链反应研究BRCA1 和 BRCA2 的DNA 甲基化。同时，用免疫印迹法、 免疫组织化学技术和共聚焦显微镜测试蛋白质的表达。我们的结果表明用18.5 μM 金雀异黄素或 78.5 μM 大豆黄酮可能扭转 DNA 的超甲基化并还原肿瘤抑制基因 BRCA1 和 BRCA2 基因的表达。5-氮杂胞苷也增强这些基因的再表达，而布地奈德却产生相反的结果。尽我们所知，这些现象，尽管需要重复，但是其对金雀异黄素和大豆黄酮可能有助于调节 BRCA1 和 BRCA2的潜在表观遗传机制提供了新的证据。未来需要研究金雀异黄素和大豆黄酮的甲基化的影响是全域的还是集中于选择的候选基因。未来需要研究金雀异黄素和大豆黄酮的甲基化的影响是全域的还是集中于选择的候选基因。