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

Authors
Ji Hoon JangKyoung-jin MinShin Kim, Jong-Wook ParkTaeg Kyu Kwon
Department
Dept. of Immunology (면역학)
Issue Date
2016
Citation
Journal of Cellular Biochemistry, Vol.117(2) : 361-369, 2016
ISSN
0730-2312
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.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/33378
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
Keimyung Author(s)
김신; 박종욱; 권택규
Full Text
http://lps3.onlinelibrary.wiley.com.proxy.dsmc.or.kr/doi/abs/10.1002/jcb.25278
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