PMID- 19154183 OWN - NLM STAT- MEDLINE DCOM- 20090414 LR - 20161125 IS - 1470-8728 (Electronic) IS - 0264-6021 (Linking) VI - 419 IP - 2 DP - 2009 Apr 15 TI - Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX. PG - 419-25 LID - 10.1042/BJ20080952 [doi] AB - 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-1alpha and the partner factor ARNT [AhR (aryl hydrocarbon receptor) nuclear translocator]. We have previously observed that HIF-1alpha 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. FAU - Takacova, Martina AU - Takacova M AD - Institute of Virology, Centre of Molecular Medicine, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic. FAU - Holotnakova, Tereza AU - Holotnakova T FAU - Vondracek, Jan AU - Vondracek J FAU - Machala, Miroslav AU - Machala M FAU - Pencikova, Katerina AU - Pencikova K FAU - Gradin, Katarina AU - Gradin K FAU - Poellinger, Lorenz AU - Poellinger L FAU - Pastorek, Jaromir AU - Pastorek J FAU - Pastorekova, Silvia AU - Pastorekova S FAU - Kopacek, Juraj AU - Kopacek J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - 0 (Antigens, Neoplasm) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Polychlorinated Dibenzodioxins) RN - 0 (Receptors, Aryl Hydrocarbon) RN - EC 4.2.1.1 (CA9 protein, human) RN - EC 4.2.1.1 (Carbonic Anhydrase IX) RN - EC 4.2.1.1 (Carbonic Anhydrases) SB - IM MH - Animals MH - Antigens, Neoplasm/genetics MH - Binding Sites MH - Blotting, Western MH - Carbonic Anhydrase IX MH - Carbonic Anhydrases/genetics/*metabolism MH - Cell Hypoxia/genetics/*physiology MH - Cell Line, Tumor MH - Chromatin Immunoprecipitation MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit MH - Mice MH - Polychlorinated Dibenzodioxins/pharmacology MH - Polymerase Chain Reaction MH - Promoter Regions, Genetic/genetics MH - Protein Binding/drug effects MH - Receptors, Aryl Hydrocarbon/genetics/metabolism/*physiology MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/drug effects EDAT- 2009/01/22 09:00 MHDA- 2009/04/15 09:00 CRDT- 2009/01/22 09:00 PHST- 2009/01/22 09:00 [entrez] PHST- 2009/01/22 09:00 [pubmed] PHST- 2009/04/15 09:00 [medline] AID - BJ20080952 [pii] AID - 10.1042/BJ20080952 [doi] PST - ppublish SO - Biochem J. 2009 Apr 15;419(2):419-25. doi: 10.1042/BJ20080952.