摘要
目的:研究三羟异黄酮(genistein)膳食暴露对SD大鼠乳腺上皮细胞基因表达谱的影响,探讨三羟异黄酮对乳腺癌的化学预防机制。方法:应用BRB-Array Tools软件对公共基因芯片数据库GEO中,三羟异黄酮膳食暴露的SD大鼠乳腺上皮细胞基因芯片表达数据进行统计学分析,找出发生变化的基因,DAVID工具进一步分析其功能及参与的生物学通路。PINA蛋白质互作平台分析这些基因的蛋白质相互作用情况。结果:得到419个差异表达基因,表达上调的175个,下调的244个,功能主要涉及钙调蛋白结合、嘌呤核苷酸结合、转录因子结合和配体依赖的核受体活性等相关的生物学过程,参与细胞信号转导。差异表达下调基因扰动的通路主要是NOD样受体信号通路,黏着斑信号通路,表皮生长因子受体信号通路,神经营养因子信号通路,均是细胞增殖、凋亡及异常的迁移能力的重要通路。上调基因扰动的通路主要是Toll样受体(toll-1ike receptor,TLR)和雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)2条途径,涉及免疫应答。结论:三羟异黄酮可能通过干扰蛋白质的磷酸化过程,影响了细胞增殖、凋亡及免疫等通路的关键分子,进而干预乳腺癌的发生。
OBJECTIVE：To investigate the influence of genistein diet on genomewide expression patterns of mam mary epithelial ceils in SD rats. METHODS： Microarray data from GEO database was used to examine the molecular chan ges. Significance Analysis of Microarray （SAM） methods was used to identify the differentially expressed genes, the dif ferentially expressed genes were annotated by DAVID a webaccessible programs with GO and KEGG. Literature mining and protein interaction analysis were then performed for these genes. RESULTS： A total of 419 genes were identified, a mong which 175 genes were upregulated and 244 downregulated. They were mainly involved in calmodulin binding, pu rine nucleotide binding, transcription factor binding,liganddependent nuclear receptor activity etc. The upregulated path ways mainly included Tolllike receptor signal and mTOR signal related to immune response. The downregulated path ways included NODlike receptor signal, Focal adhesion, ErbB signal, Neurotrophin signal etc. CONCLUSIONS： The data suggest that genistein can widely modulate gene expression pattern of signal transducers. They are mainly involved in cell proliferation, cell apoptosis, cell migration,immune response and so on. Immune mechanism may be a new molecular detec tion of chemoprophylactic effects. These results will bring new insights into chemoprevention mechanisms of genistein.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2014年第12期890-893,共4页
Chinese Journal of Cancer Prevention and Treatment
基金
四川省卫生厅基金(120491)
成都医学院创新性实验项目(CX201232)
成都医学院教育教学改革项目(JG201311)
