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Title: Lipocalin 2, a new GADD153 target gene, as an apoptosis inducer of endoplasmic reticulum stress in lung cancer cells

Abstract

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. Highlights: ► We demonstrate that Lipocalin 2 is a new GADD153 target gene. ► Lipocalin 2 mediates ER stress-induced apoptosis. ► ER stress-induced lipocalin 2 expression is calcium-independent in A549 cells. ► Lipocalin 2 dose not play a major role in ER stress-induced autophagy.

Authors:
;  [1];  [2];  [3]; ;  [1];  [4];  [1]
  1. Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 40201, Taiwan (China)
  2. Division of Chest Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan (China)
  3. Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan (China)
  4. Department of Thoracic Surgery, Veterans General Hospital—Taichung, Taichung 40705, Taiwan (China)
Publication Date:
OSTI Identifier:
22215911
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 263; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CALCIUM; CHROMATIN; DNA; DOSES; ENDOPLASMIC RETICULUM; GENES; LUNGS; NEOPLASMS; PROMOTERS; TOXICITY; TRANSCRIPTION FACTORS

Citation Formats

Hsin, I-Lun, Hsiao, Yueh-Chieh, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Wu, Ming-Fang, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Jan, Ming-Shiou, Tang, Sheau-Chung, Lin, Yu-Wen, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Hsu, Chung-Ping, Department of Surgery, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, Taipei 11221, Taiwan, Ko, Jiunn-Liang, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, and Division of Chest Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. Lipocalin 2, a new GADD153 target gene, as an apoptosis inducer of endoplasmic reticulum stress in lung cancer cells. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.07.005.
Hsin, I-Lun, Hsiao, Yueh-Chieh, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Wu, Ming-Fang, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Jan, Ming-Shiou, Tang, Sheau-Chung, Lin, Yu-Wen, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Hsu, Chung-Ping, Department of Surgery, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, Taipei 11221, Taiwan, Ko, Jiunn-Liang, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, & Division of Chest Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. Lipocalin 2, a new GADD153 target gene, as an apoptosis inducer of endoplasmic reticulum stress in lung cancer cells. United States. https://doi.org/10.1016/J.TAAP.2012.07.005
Hsin, I-Lun, Hsiao, Yueh-Chieh, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Wu, Ming-Fang, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Jan, Ming-Shiou, Tang, Sheau-Chung, Lin, Yu-Wen, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, Hsu, Chung-Ping, Department of Surgery, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, Taipei 11221, Taiwan, Ko, Jiunn-Liang, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan, and Division of Chest Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. 2012. "Lipocalin 2, a new GADD153 target gene, as an apoptosis inducer of endoplasmic reticulum stress in lung cancer cells". United States. https://doi.org/10.1016/J.TAAP.2012.07.005.
@article{osti_22215911,
title = {Lipocalin 2, a new GADD153 target gene, as an apoptosis inducer of endoplasmic reticulum stress in lung cancer cells},
author = {Hsin, I-Lun and Hsiao, Yueh-Chieh and Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan and Wu, Ming-Fang and School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan and Jan, Ming-Shiou and Tang, Sheau-Chung and Lin, Yu-Wen and Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan and Hsu, Chung-Ping and Department of Surgery, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, Taipei 11221, Taiwan and Ko, Jiunn-Liang and Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan and Division of Chest Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan},
abstractNote = {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. Highlights: ► We demonstrate that Lipocalin 2 is a new GADD153 target gene. ► Lipocalin 2 mediates ER stress-induced apoptosis. ► ER stress-induced lipocalin 2 expression is calcium-independent in A549 cells. ► Lipocalin 2 dose not play a major role in ER stress-induced autophagy.},
doi = {10.1016/J.TAAP.2012.07.005},
url = {https://www.osti.gov/biblio/22215911}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 263,
place = {United States},
year = {Sat Sep 15 00:00:00 EDT 2012},
month = {Sat Sep 15 00:00:00 EDT 2012}
}