Lipocalin 2, a new GADD153 target gene, as an apoptosis inducer of endoplasmic reticulum stress in lung cancer cells.
Endoplasmic reticulum (ER) stress is activated under severe cellular conditions. GADD153, a member of the C/EBP family, is an unfolded protein response (UPR) responsive transcription factor. Increased levels of lipocalin 2, an acute phase protein, have been found in several epithelial cancers. The aim of this study is to investigate the function of lipocalin 2 in lung cancer cells under ER stress. Treatment with thapsigargin, an ER stress activator, led to increases in cytotoxicity, ER stress, apoptosis, and lipocalin 2 expression in A549 cells. GADD153 silencing decreased lipocalin 2 expression in A549 cells. On chromatin immunoprecipitation assay, ER stress increased GADD153 DNA binding to lipocalin 2 promoter. Furthermore, silencing of lipocalin 2 mitigated ER stress-mediated apoptosis in A549 cells. Our findings demonstrated that lipocalin 2 is a new GADD153 target gene that mediates ER stress-induced apoptosis.
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 40201, Taiwan.
I-Lun
IL
Hsin
Yueh-Chieh
YC
Hsiao
Ming-Fang
MF
Wu
Ming-Shiou
MS
Jan
Sheau-Chung
SC
Tang
Yu-Wen
YW
Lin
Chung-Ping
CP
Hsu
Jiunn-Liang
JL
Ko
D000209:Acute-Phase Proteins / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000235:genetics*
D000209:Acute-Phase Proteins; C497249:DDIT3 protein, human; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D051742:Transcription Factor CHOP; D019284:Thapsigargin