Barve Avantika, Khor Tin Oo, Nair Sujit, Lin Wen, Yu Siwang, Jain Mohit Raja, Chan Jefferson Y, Kong Ah-Ng
Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
J Pharm Sci. 2008 Oct;97(10):4528-45. doi: 10.1002/jps.21311.
The involvement of Nrf2-a bZip transcription factor in soy isoflavones induced protection against oxidative stress and cancer has been reported. To gain better insight into the role of Nrf2 in prostate cancer chemoprevention by soy isoflavones, we examined the pharmacogenomics and gene expression profiles elicited by soy isoflavones in the prostates of C57BL/6J/Nrf2(-/-) and C57BL6J/Nrf2(+/+) wildtype. The profiles were analyzed using 45000 Affymetrix mouse genome 430-2.0 array and Genespring-7.2 software. The results obtained from microarray were further validated by real-time reverse transcription-PCR. Clusters of genes that were induced or suppressed more than twofold were identified as Nrf2 regulated soy isoflavone induced or suppressed genes. Classification based on their biological function revealed that genes mainly belonging to the categories of electron transport, phase II metabolizing enzymes, cell growth and differentiation, apoptosis, cell cycle, transcription factors, transport, mRNA processing, and carbohydrate homeostasis were either induced or suppressed by soy isoflavone and regulated by Nrf2. In addition, modulation of novel target genes such as LATS2 and GREB1 were identified to be mediated by Nrf2. Thus our current study provides a potential link between cancer chemopreventive properties of soy derived phytochemicals, the transcription factor Nrf2 and prevention of prostate cancer.
已有报道称，Nrf2（一种碱性亮氨酸拉链转录因子）参与大豆异黄酮诱导的抗氧化应激和抗癌保护作用。为了更深入了解Nrf2在大豆异黄酮预防前列腺癌中的作用，我们研究了C57BL/6J/Nrf2（-/-）和C57BL6J/Nrf2（+/+）野生型小鼠前列腺中大豆异黄酮引发的药物基因组学和基因表达谱。使用45000个Affymetrix小鼠基因组430 - 2.0芯片和Genespring - 7.2软件对这些谱进行分析。通过实时逆转录 - PCR进一步验证从微阵列获得的结果。诱导或抑制超过两倍的基因簇被鉴定为Nrf2调控的大豆异黄酮诱导或抑制基因。根据其生物学功能进行分类显示，主要属于电子传递、II相代谢酶、细胞生长和分化、细胞凋亡、细胞周期、转录因子、转运、mRNA加工和碳水化合物稳态等类别的基因，要么被大豆异黄酮诱导或抑制，并受Nrf2调控。此外，还确定了诸如LATS2和GREB1等新靶基因的调节是由Nrf2介导的。因此，我们目前的研究提供了大豆衍生植物化学物质的癌症化学预防特性、转录因子Nrf2与前列腺癌预防之间的潜在联系。
