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| Status |
Public on Apr 30, 2014 |
| Title |
The orphan nuclear receptor NR4A1 (Nur77, TR3) regulates oxidative and endoplasmic reticulum stress in pancreatic cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
NR4A1 (Nur77, TR3) is an orphan nuclear receptor that is overexpressed in pancreatic cancer cells and tumors and exhibits pro-oncogenic activity. Knockdown of NR4A1 by RNA interference (siNR4A1) in Panc1 cells and analysis of the proteome resulted in induction of several markers of endoplasmic reticulum (ER) stress including glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein-homologous protein (CHOP), activating transcription factor-3 (ATF-3) and AFT-6. These effects were accompanied by induction of apoptosis and similar results were observed after treatment of pancreatic cancer cells with the known inactivator of NR4A1, 1,1-bis(3’-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH). Both siNR4A1 (transfected) and DIM-C-pPhOH also induced reactive oxygen species (ROS) and induction of ROS and ER stress by these agents was attenuated after cotreatment with antioxidants. Transfection of Panc1 cells with siNR4A1 follow by analysis of gene expression by arrays identified ROS metabolism genes regulated by NR4A1. Knockdown of one of these genes, thioredoxin domain containing 5 (TXNDC5) also resulted in induction of ROS and ER stress demonstrating that NR4A1 regulates levels of ER stress and ROS in pancreatic cancer cells to facilitate cell proliferation and survival. Inactivation of this receptor by siNR4A1 or DIM-C-pPhOH decreases TXNDC5 resulting in activation of ROS/ER stress and pro-apoptotic pathways and represents a novel pathway for inducing cell death in pancreatic cancer cells.
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| Overall design |
Two groups of samples are included: 1. siControl; 2. siNR4A1 treatment in PAC1 cell. Transfection of Panc1 cells with siNR4A1 follow by analysis of gene expression by arrays identified ROS metabolism genes regulated by NR4A1.
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| |
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| Contributor(s) |
Lee S, Lee J, Safe S |
| Citation(s) |
24515801 |
| Submission date |
May 16, 2013 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Sangbae Kim |
| E-mail(s) |
sangbkim22@gmail.com
|
| Organization name |
Baylor Colleage of Medicine
|
| Department |
HGSC
|
| Street address |
1 Baylor plaza
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA203248 |
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