Yi Yong Weon, Oh Seunghoon
Department of Nanobiomedical Science, Graduate School, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam 330-714 Republic of Korea.
Department of Physiology, College of Medicine, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam 330-714 Republic of Korea.
Genes Genomics. 2015;37(1):97-109. doi: 10.1007/s13258-014-0253-2. Epub 2014 Dec 5.
NRF2 is a nuclear transcription factor activated in response to oxidative stress and related with metabolizing of xenotoxic materials and ABC transporter mediated drug resistance. We studied the expression of mRNAs under the siRNA-mediated knockdown of NRF2 and tBHQ-treated condition in AsPC-1 metastatic pancreatic cancer cell line to understand the AsPC-1 specific role(s) of NRF2 and further to investigate the relationship between drug resistance and metastatic plasticity and mobility of AsPc1. Here we show that the genes of aldo-keto reductases, cytochrome P450 family, aldehyde dehydrogenase, thioredoxin reductase, ABC transporter and epoxide hydrolase responsible for drug metabolism or oxidative stress concisely responded to NRF2 stabilization and knockdown of . In addition the expression of , a candidate of oncogene and , a suppressor of metastasis were affected by NRF2 stabilization and knockdown. Our result provide comprehensive understanding of NRF2 target genes of drug response, oxidative stress response and metastasis in AsPc-1 metastatic pancreatic cancer cell line.
NRF2是一种核转录因子，在氧化应激反应中被激活，与异源毒性物质的代谢以及ABC转运蛋白介导的耐药性有关。我们研究了在AsPC-1转移性胰腺癌细胞系中，在小干扰RNA介导的NRF2敲低和叔丁基对苯二酚处理条件下mRNA的表达，以了解NRF2在AsPC-1中的特定作用，并进一步研究耐药性与AsPc1转移可塑性和迁移性之间的关系。在此我们表明，负责药物代谢或氧化应激的醛酮还原酶、细胞色素P450家族、醛脱氢酶、硫氧还蛋白还原酶、ABC转运蛋白和环氧化物水解酶的基因对NRF2的稳定和敲低有简洁的反应。此外，癌基因候选物和转移抑制物的表达受NRF2稳定和敲低的影响。我们的结果为AsPc-1转移性胰腺癌细胞系中药物反应、氧化应激反应和转移的NRF2靶基因提供了全面的理解。
