Journal of Medicinal Food, 2011, 14(6):584-93.

The Dietary Compounds Resveratrol and Genistein Induce Activating Transcription Factor 3 While Suppressing Inhibitor of DNA Binding/Differentiation-1

Frank G. Bottone, Jr and Brenda Alston-Mills

North Carolina State University, College of Agriculture and Life Sciences, Department of Animal Sciences, Raleigh, North Carolina, USA; et al

Various chemopreventive compounds alter gene expression, possibly explaining their biological activity. One gene induced by a variety of chemopreventive compounds is the one coding for the transcription factor activating transcription factor 3 (ATF3). In this study, we performed microarray analysis on mRNA isolated from human colorectal cancer cells overexpressing ATF3 to ascertain the biological activity of this gene in cancer. As a result, 64 genes were induced or repressed. One gene identified by microarray analysis as repressed by overexpression of ATF3 was inhibitor of DNA binding/differentiation-1 (Id1). Id1 is important to cell growth and proliferation and therefore may represent an important downstream target of ATF3 responsible for the biological activity of ATF3. Id1 interacts with ATF3, thereby sequestering its activity, making it an ideal candidate for further study. The induction of ATF3 and repression of Id1 in these cells were confirmed at the mRNA and protein levels by semiquantitative real-time reverse transcription-polymerase chain reaction and western blot analysis, respectively. To determine if the repression of Id1 seen following microarray analysis of these cells occurred following treatment with dietary compounds with known chemotherapeutic activity, human colorectal cancer cells were treated with resveratrol and genistein, and their expression was determined. As a result, ATF3 was induced, and Id1 was repressed, by these compounds and by sulindac sulfide, a positive control, at the mRNA and protein level. Further work is needed to determine the molecular mechanism(s) responsible for the regulation of Id1 and to determine if biological activity of ATF3 overexpression is mediated by repression of Id1 by these compounds.

美国《药膳杂志》，2011年6月

膳食化合物白藜芦醇和染料木黄酮诱导激活转录因子 3 同时抑制DNA 绑定/分化-1抑制因子

小弗兰克 G 波特内和布伦达 奥尔斯顿 米尔斯

美国北卡罗莱纳州大学农业和生命科学学院

多种化学防癌化合物改变基因的表达，可能解释其生物活性。多种化学防癌化合物诱导的基因是一种转录因子激活转录因子 3 (ATF3)的编码。在此研究中，我们对从人体结肠癌细胞中分离的mRNA特异性表达 ATF3进行了芯片分析来确定这种基因在癌症中的生物活性。其结果是，64 个基因被诱导或抑制。基因芯片分析确定的基因当 ATF3 过表达抑制时是 DNA 绑定/分化-1 (Id1)的 抑制剂。Id1 对细胞的生长和扩散非常重要，并且因此可能代表了一个重要的ATF3下游目标来负责 ATF3 的生物活性。Id1与 ATF3相互作用，从而封存其活性，使其成为进一步研究的理想选择。在这些细胞中，通过半定量实时逆转录-聚合酶链反应和免疫印迹分析分别确定ATF3 诱导和Id1抑制的 mRNA 和蛋白水平。为了检测在微阵列分析这些细胞经过具有显著化学防癌活性的膳食化合物治疗后Id1的抑制是否发生，用白藜芦醇及染料木黄酮治疗人体结肠癌细胞，并测试它们的表达。因此，通过这些化合物和硫化舒林酸积极控制mRNA 和蛋白水平，ATF3被诱导， Id1 被抑制。需要进一步的工作以确定负责 Id1 调控的分子机制，并且确定这些化合物是否能通过Id1 的抑制来介导ATF3 生物活性的过表达。