Thioredoxin-1 modulates transcription of cyclooxygenase-2 via hypoxia-inducible factor-1alpha in non-small cell lung cancer
- PMID: 16397226
- DOI: 10.1158/0008-5472.CAN-05-1357
Thioredoxin-1 modulates transcription of cyclooxygenase-2 via hypoxia-inducible factor-1alpha in non-small cell lung cancer
Abstract
Hypoxic induction of gene expression occurs mainly via the hypoxia-inducible factor-1 (HIF-1) transcription factor and is a critical step in tumor growth. Cyclooxygenase-2 (COX-2) is commonly overexpressed in non-small cell lung cancer (NSCLC). In this study, we sought to determine the role of HIF-1 in the induction of COX-2 expression during hypoxia. Through sequence comparison of hypoxia-responsive genes, COX-2 promoter deletion analysis, and site-directed mutagenesis, we identified a hypoxia-responsive element within the COX-2 promoter that interacts with HIF-1alpha and underlies the mechanism of hypoxic activation of COX-2 in lung cancer cells. Proteomic analysis of NSCLC identified thioredoxin-1 as a redox protein overexpressed in NSCLC correlated with poor prognosis. We also show that thioredoxin-1 stabilizes HIF-1alpha to induce hypoxia-responsive genes under normoxic conditions. Our results identify two new mechanisms for regulation of COX-2 expression in NSCLC.
Similar articles
-
Direct transcriptional up-regulation of cyclooxygenase-2 by hypoxia-inducible factor (HIF)-1 promotes colorectal tumor cell survival and enhances HIF-1 transcriptional activity during hypoxia.Cancer Res. 2006 Jul 1;66(13):6683-91. doi: 10.1158/0008-5472.CAN-06-0425. Cancer Res. 2006. PMID: 16818642
-
Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1alpha gene.Cancer Chemother Pharmacol. 2006 Dec;58(6):776-84. doi: 10.1007/s00280-006-0224-7. Epub 2006 Mar 11. Cancer Chemother Pharmacol. 2006. PMID: 16532342
-
Endothelin-1 and endothelin-3 promote invasive behavior via hypoxia-inducible factor-1alpha in human melanoma cells.Cancer Res. 2007 Feb 15;67(4):1725-34. doi: 10.1158/0008-5472.CAN-06-2606. Cancer Res. 2007. PMID: 17308114
-
Hypoxia-inducible factor-1 in human breast and prostate cancer.Endocr Relat Cancer. 2006 Sep;13(3):739-49. doi: 10.1677/erc.1.00728. Endocr Relat Cancer. 2006. PMID: 16954428 Review.
-
Interactions between hypoxia and epidermal growth factor receptor in non-small-cell lung cancer.Clin Lung Cancer. 2006 Jan;7(4):250-6. doi: 10.3816/CLC.2006.n.002. Clin Lung Cancer. 2006. PMID: 16512978 Review.
Cited by
-
Combination of physical activity, nutrition, or other metabolic factors and vaccine response.Front Biosci. 2007 Sep 1;12:4997-5029. doi: 10.2741/2444. Front Biosci. 2007. PMID: 17569626 Free PMC article. Review.
-
The effect of alendronate on proteome of hepatocellular carcinoma cell lines.Int J Proteomics. 2014;2014:532953. doi: 10.1155/2014/532953. Epub 2014 Feb 6. Int J Proteomics. 2014. PMID: 24653834 Free PMC article.
-
[The expression and clinical significance of HIF-1α, COX-2 and E-cadherin in patients with lung adenocarcinoma].Zhongguo Fei Ai Za Zhi. 2011 Mar;14(3):219-26. doi: 10.3779/j.issn.1009-3419.2011.03.07. Zhongguo Fei Ai Za Zhi. 2011. PMID: 21426663 Free PMC article. Chinese.
-
Analysis of the in vitro effects of di-(2-ethylhexyl) phthalate exposure on human uterine leiomyoma cells.Exp Ther Med. 2018 Jun;15(6):4972-4978. doi: 10.3892/etm.2018.6040. Epub 2018 Apr 10. Exp Ther Med. 2018. PMID: 29805520 Free PMC article.
-
Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1.Theranostics. 2017 Mar 23;7(5):1389-1406. doi: 10.7150/thno.17647. eCollection 2017. Theranostics. 2017. PMID: 28435473 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
