Tumour-associated expression of CA IX (carbonic anhydrase IX) is to a major extent regulated by HIF-1 (hypoxia-inducible factor-1) which is important for transcriptional activation and consists of the oxygen-regulated subunit HIF-1α and the partner factor ARNT [AhR (aryl hydrocarbon receptor) nuclear translocator]. We have previously observed that HIF-1α competes with the AhR for interaction with ARNT under conditions when both conditionally regulated factors are activated. We have therefore investigated whether TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)-induced activation of the AhR pathway might interfere with CA IX expression. The results from the present study suggest that TCDD treatment reduces hypoxic induction of both CA IX mRNA and protein expression. Moreover, the transcriptional activity of the CA9 promoter was significantly reduced by expression of CAAhR (constitutively active AhR), which activates transcription in a ligand-independent manner. Finally, we found that ARNT is critical for both hypoxic induction and the TCDD-mediated inhibition of CA9 expression.
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Research Article|
March 27 2009
Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX
Martina Takacova;
Martina Takacova
1
*Institute of Virology, Centre of Molecular Medicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic
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Tereza Holotnakova;
Tereza Holotnakova
1
*Institute of Virology, Centre of Molecular Medicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic
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Jan Vondracek;
Jan Vondracek
†Department of Cytokinetics, Institute of Biophysics, AS CR, Kralovopolska 135, 612 65 Brno, Czech Republic
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Miroslav Machala;
Miroslav Machala
‡Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic
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Katerina Pencikova;
Katerina Pencikova
‡Department of Chemistry and Toxicology, Veterinary Research Institute, Hudcova 70, 621 00 Brno, Czech Republic
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Katarina Gradin;
Katarina Gradin
§Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden
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Lorenz Poellinger;
Lorenz Poellinger
§Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden
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Jaromir Pastorek;
Jaromir Pastorek
*Institute of Virology, Centre of Molecular Medicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic
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Silvia Pastorekova;
Silvia Pastorekova
*Institute of Virology, Centre of Molecular Medicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic
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Juraj Kopacek
Juraj Kopacek
2
*Institute of Virology, Centre of Molecular Medicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic
2To whom correspondence should be addressed (email virukopa@savba.sk).
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Publisher: Portland Press Ltd
Received:
September 15 2008
Revision Received:
January 16 2009
Accepted:
January 20 2009
Accepted Manuscript online:
January 20 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 419 (2): 419–425.
Article history
Received:
September 15 2008
Revision Received:
January 16 2009
Accepted:
January 20 2009
Accepted Manuscript online:
January 20 2009
Citation
Martina Takacova, Tereza Holotnakova, Jan Vondracek, Miroslav Machala, Katerina Pencikova, Katarina Gradin, Lorenz Poellinger, Jaromir Pastorek, Silvia Pastorekova, Juraj Kopacek; Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX. Biochem J 15 April 2009; 419 (2): 419–425. doi: https://doi.org/10.1042/BJ20080952
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