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Wohlkoenig, C; Leithner, K; Olschewski, A; Olschewski, H; Hrzenjak, A.
TR3 is involved in hypoxia-induced apoptosis resistance in lung cancer cells downstream of HIF-1α.
Lung Cancer. 2017; 111(3):15-22
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Hrzenjak Andelko
Leithner Katharina
Olschewski Andrea
Olschewski Horst
Wohlkönig Christoph
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Abstract:
Lung cancer is the leading cause of cancer death worldwide. Like in all solid tumors, hypoxia is common in lung cancer and contributes to apoptosis, and thus chemotherapy resistance. However, the underlying mechanisms are not entirely clear. TR3 (NR4A1, Nur77) is an orphan nuclear receptor that induces apoptosis and may mediate chemotherapy-induced apoptosis in cancer cells. We used A549, H23 and H1299 cell lines to investigate how TR3-mediated apoptosis is affected by hypoxia in non-small cell lung cancer (NSCLC) cells. Cell culture, western blot analysis, apoptosis assay, and siRNA-mediated gene silencing were performed in this study. The TR3 activator cytosporone B was used to investigate TR3-mediated apoptosis in NSCLC cells under normoxic and hypoxic conditions. Cytosporone B induced apoptosis in a concentration-dependent manner. Chronic moderate hypoxia induced a significant down-regulation of TR3. Accordingly, the cytosporone B effect was reduced under these conditions. Hypoxia-induced down-regulation of TR3 was mediated by hypoxia-inducible factor 1α. Our immunoblotting analysis and expression data from a public dataset suggest that TR3 is downregulated in NSCLC. In conclusion, our findings suggest that hypoxia-induced down-regulation of TR3 might play an important role for hypoxia-induced apoptosis resistance in NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Apoptosis - genetics
Cell Line, Tumor -
Cell Survival - genetics
Gene Expression Regulation, Neoplastic -
Gene Silencing -
Humans -
Hypoxia - genetics
Hypoxia - metabolism
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Nuclear Receptor Subfamily 4, Group A, Member 1 - agonists
Nuclear Receptor Subfamily 4, Group A, Member 1 - genetics
Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism
Protein Processing, Post-Translational -
RNA Interference -
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA, Small Interfering - genetics

Find related publications in this database (Keywords)
Non-small cell lung cancer
Hypoxia
Apoptosis
TR3
HIF-1 alpha
Cytosporone B
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