@article{e3b32b99214c48cdb3eb52decd81f6cf,
title = "Inflammation, but not hypoxia, mediated HIF-1α activation depends on COX-2",
abstract = "The COX pathway has been a target for pharmaceutical intervention in diseases with a high inflammatory component ranging from asthma and Alzheimer's to arthritis and cancer. A major transcriptional promoter of the malignant phenotype, HIF-1α, has been observed to be regulated by the COX-2 product PGE2. Here we show that HIF-1α protein significantly accumulated in human breast cancer MDA-MB-231 cells in response to the pro-inflammatory cytokine IL-1β, but not in COX-2-silenced MDA-MB-231 cells. In contrast HIF-1α expression could be detected in COX-2-silenced cells in response to the hypoxia-mimetic agent CoCl2 and hypoxia. Gene expression profiling in COX-2-containing and COX-2-silenced cells showed that the hypoxia-induced transcriptional response is largely unaffected by COX-2 silencing. These data suggest that the profound effects of COX-2 silencing on inhibiting invasion, tumor growth and metastasis from MDA-MB-231 cells are dependent on the induction of IL-1β-dependent COX-2 and HIF-1α but are independent of hypoxia.",
keywords = "Breast cancer, COX-2, COX-2-silencing, HIF-1α, Hypoxia, Inflammation",
author = "Ioannis Stasinopoulos and O'Brien, {David R.} and Bhujwalla, {Zaver M.}",
note = "Funding Information: purchased from Qiagen{\textquoteright}s geneglobe collection and they are cata-This work was supported by NIH research grants 2R01CA82337 Glunde for useful discussions and advice. logue numbers: QT00223188, QT01036861, QT00068957 and and P50 CA103175. QT00001687 respectively. Fold differences werBioscience. e calculated using the 2ΔΔCtmethod. References Microarray analysis. RNA from COX-2-containing (MDA-MB-angiogenesis and normalization. Microvasc Res 2007; 74:72-84.1.Fukumura D, Jain RK. Tumor microvasculature and microenvironment: targets for anti- 231) and COX-2-silenced (Clone 2 and Pooled) cells was isolated Naumov GN, Akslen LA, Folkman J. Role of angiogenesis in human tumor dormancy: as described above. Samples were subjected to agarose formaldehyde animal models of the angiogenic switch. Cell Cycle 2006; 5:1779-87. electrophoresis to determine the quality of the RNA by comparing loop-helix-PAS heterodimer regulated by cellular Otension. Proc Natl Acad Sci USA Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix- the ratios of 18S and 28S RNA species. All samples were run 1995; 92:5510-4. 2 in commercial arrays from Affymetrix (Santa Clara, CA), using Huang LE, Gu J, Schau M, Bunn HF. Regulation of hypoxia-inducible factor 1alpha is Human Genome U133Plus 2.0 GeneChip arrays as described in the Proc Natl Acad Sci USA 1998; 95:7987-92.mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Landes Affymetrix web site (http://www.affymetrix.com). Probe hybridiza-Liao D, Johnson RS. Hypoxia: a key regulator of angiogenesis in cancer. Cancer Metastasis tion and analysis was run as suggested by the manufacturer in the Rev 2007; 26:281-90. aforementioned website. These descriptions include all information HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell Zhang H, Gao P, Fukuda R, Kumar G, Krishnamachary B, Zeller KI, Dang CV, Semenza GL. currently considered under the MIAME supportive guidelines, with carcinoma by repression of C-MYC activity. Cancer Cell 2007; 11:407-20. which the JHMI Microarray Core Facility abides in all its procedures. in tumor progression: the role of tumor-associated macrophages. Crit Rev Oncol Hematol Allavena P, Sica A, Solinas G, Porta C, Mantovani A. The inflammatory micro-environment Expression signals were obtained by Robust Multiarray Analysis.2008; 66:1-9.16 {\textcopyright}The posterior probabilities of the differential expression of genes Apte RN, Dotan S, Elkabets M, White MR, Reich E, Carmi Y, Song X, Dvozkin T, Krelin Y, 2be0twe0en9 th e treatments were estimated with an empirical Bayses tumor-host interactions. Cancer Metastasis Rev 2006; 25:387-408.Voronov E. The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and",
year = "2009",
month = jan,
doi = "10.4161/cbt.8.1.7079",
language = "English (US)",
volume = "8",
pages = "31--35",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "1",
}