| Hypoxia induced expression of endogenous markers in vitro is highly influenced by pH. | |
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MedLine Citation:
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PMID: 17512623 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Genes such as carbonic anhydrase IX (Ca9), glucose transporter 1 (Glut1), lactate dehydrogenase A (LDH-A), osteopontin (OPN) and lysyl oxidase (LOX) have been suggested as hypoxic markers, but inconsistent results suggest that factors other than oxygen influence their expression. The current study is a detailed investigation using a range of pH values from 6.3 to 7.5 in two human cell lines to establish the pH dependency of hypoxia induced gene expression. METHODS: Human tumour cell lines (uterine cervix squamous cell carcinoma (SiHa) and pharyngeal squamous cell carcinoma [FaDu(DD)]) were used. Hypoxia was induced by gassing cells in airtight chambers with various oxygen concentrations (21%, 1%, 0.1%, 0.01% and 0%) for up to 24h. The media were titrated to a range of pH values (7.5, 7.0, 6.7, 6.5 and 6.3). Gene expression was determined by real-time PCR. RESULTS: In both SiHa and FaDu(DD) cells Ca9 and LOX reached the highest level of expression at 1% oxygen. In FaDu(DD) cells, a pH of 6.5 had a medium suppression effect on the hypoxia induced expression of Ca9. pH 6.3 resulted in severe suppression of expression for Ca9 and LOX in both SiHa and FaDu(DD). Glut1 and LDH-A had a similar expression pattern to each other, with a maximum expression at 0.01% oxygen, in both cell lines. For these genes pH 6.5 and 6.3 changed the expression pattern in SiHa cells. OPN was up regulated at low oxygen in SiHa cells, but was not induced by hypoxia in FaDu(DD) cells. CONCLUSION: As tumour hypoxia occurs in a deprived microenvironment, other environmental factors, for example low pH, might interact with the effect of low oxygen concentration on gene expression. This study shows that pH in two cell lines has a profound influence on the oxygen dependent induction of certain endogenous hypoxic markers. |
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Authors:
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Brita Singers Sørensen; Jan Alsner; Jens Overgaard; Michael R Horsman |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-05-18 |
Journal Detail:
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Title: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Volume: 83 ISSN: 0167-8140 ISO Abbreviation: Radiother Oncol Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-06-20 Completed Date: 2008-03-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8407192 Medline TA: Radiother Oncol Country: Ireland |
Other Details:
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Languages: eng Pagination: 362-6 Citation Subset: IM |
Affiliation:
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Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. bsin@oncology.dk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, Neoplasm
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blood,
metabolism Biological Markers / metabolism* Carbonic Anhydrases / blood, metabolism Cell Hypoxia / genetics* Cell Line Cell Line, Tumor Female Gene Expression Regulation* Humans Hydrogen-Ion Concentration Male Osteopontin / blood, metabolism Oxygen / physiology* RNA, Messenger / biosynthesis Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Neoplasm; 0/Biological Markers; 0/RNA, Messenger; 106441-73-0/Osteopontin; 7782-44-7/Oxygen; EC 4.2.1.1/CA9 protein, human; EC 4.2.1.1/Carbonic Anhydrases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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