Mulvey Laura, Chandrasekaran Alamelu, Liu Kai, Lombardi Sarah, Wang Xue-Ping, Auborn Karen J, Goodwin Leslie
Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
Mol Med. 2007 Jan-Feb;13(1-2):69-78. doi: 10.2119/2006-00038.Mulvey.
Diindolylmethane (DIM), a biologically active congener of indole-3-carbinol (I3C) derived from cruciferous vegetables, is a promising agent for the prevention of estrogen-sensitive cancers. Both DIM and estrogen affect transcription of genes by binding receptors, such as aryl hydrocarbon receptor (AhR) or estrogen receptors (ER). Gene regulation by DIM and estradiol (E2) can be very complex. While DIM typically binds the AhR, this complex can directly associate with the ER, recruit co-activators that bind to estrogen-responsive promoters, and activate transcription. Alternately, DIM can bind the ER directly. In this study, we have analyzed gene expression using microarray profiling and quantitative real time-polymerase chain reaction in MCF7 breast cancer cells treated with E2 (1 nM) or DIM (25 microM) alone or in combination for 16 h. The interplay of E2 and DIM was reflected in the expression of a subset of genes (<90) in which the combination of E2 and DIM acted either additively or antagonistically to alter gene expression.
二吲哚甲烷（DIM）是一种源自十字花科蔬菜的吲哚 - 3 - 甲醇（I3C）的生物活性同系物，是预防雌激素敏感性癌症的一种有前景的药物。DIM和雌激素都通过与受体结合来影响基因转录，如芳烃受体（AhR）或雌激素受体（ER）。DIM和雌二醇（E2）对基因的调控可能非常复杂。虽然DIM通常与AhR结合，但这种复合物可以直接与ER结合，募集与雌激素反应性启动子结合的共激活因子，并激活转录。或者，DIM也可以直接与ER结合。在本研究中，我们使用基因芯片分析和定量实时聚合酶链反应，分析了单独或联合使用E2（1 nM）或DIM（25 μM）处理16小时的MCF7乳腺癌细胞中的基因表达。E2和DIM的相互作用反映在一组基因（<90个）的表达中，其中E2和DIM的组合对基因表达的影响呈相加或拮抗作用。
