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RU486 Induces Pro-Apoptotic Endoplasmic Reticulum Stress Through the Induction of CHOP Expression by Enhancing C/EBPδ Expression in Human Renal Carcinoma Caki Cells

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Author(s)
Ji Hoon JangKyoung-jin MinShin Kim, Jong-Wook ParkTaeg Kyu Kwon
Keimyung Author(s)
Kim, ShinPark, Jong WookKwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Journal of Cellular Biochemistry
Issued Date
2016
Volume
117
Issue
2
Abstract
RU486 (Mifepristone) is known as an antagonist of the progesterone receptor and glucocorticoid receptor. Here, we investigated the
mechanism underlying anti-tumor activity of RU486 in renal carcinoma Caki cells. Treatment of Caki cells with RU486 was found to induce
several signature ER stress markers; including ER stress-specific XBP1 splicing, and the up-regulation of glucose-regulated protein (GRP)-78
and CCAAT/enhancer-binding protein homologous protein (CHOP) expression. RU486-induced expression of CHOP involves the putative
C/EBPd site within the CHOP promoter region. Using a combination of C/EBPd cDNA transfection, the luciferase assay with a mutated C/EBPd
binding site and siRNA-mediated C/EBPd knockdown, we found that the C/EBPd site is required for RU486-mediated activation of the CHOP
promoter. In addition, RU486-induced CHOP expression is down-regulated by inhibition of the p38 MAPK and JNK signaling pathways at the
post-translational levels. RU486 dose-dependently induced apoptotic cell death in renal carcinoma cells. Suppression of CHOP expression by
CHOP siRNA attenuated RU486-induced apoptosis. Taken together, RU486 induces pro-apoptotic ER stress through the induction of CHOP
expression.
Keimyung Author(s)(Kor)
김신
박종욱
권택규
Publisher
School of Medicine
Citation
Ji Hoon Jang et al. (2016). RU486 Induces Pro-Apoptotic Endoplasmic Reticulum Stress Through the Induction of CHOP Expression by Enhancing C/EBPδ Expression in Human Renal Carcinoma Caki Cells. Journal of Cellular Biochemistry, 117(2), 361–369. doi: 10.1002/jcb.25278
Type
Article
ISSN
0730-2312
Source
http://lps3.onlinelibrary.wiley.com.proxy.dsmc.or.kr/doi/abs/10.1002/jcb.25278
DOI
10.1002/jcb.25278
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33378
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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