Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX

Martina Takacova , Tereza Holotnakova , Jan Vondracek , Miroslav Machala , Katerina Pencikova , Katarina Gradin , Lorenz Poellinger , Jaromir Pastorek , Silvia Pastorekova , Juraj Kopacek (1)

1 Institute of Virology

Tumor-associated expression of carbonic anhydrase IX (CA IX) is to a major extent regulated by hypoxia inducible factor-1 (HIF-1) which is important for transcriptional activation and consists of the oxygen-regulated subunit HIF-1α and the partner factor ARNT. We have previously observed that HIF-1α competes with the aryl hydrocarbon receptor (AhR) for interaction with aryl hydrocarbon nuclear translocator (ARNT) under conditions when both conditionally regulated factors are activated. We have therefore investigated whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of the AhR pathway might interfere with CA IX expression. Our data 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 constitutively active AhR (CAAhR), 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.

Mots clés: Life Sciences

Martina Takacova, Tereza Holotnakova, Jan Vondracek, Miroslav Machala, Katerina Pencikova, et al.. Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX. Biochemical Journal, 2009, 419 (2), pp.419-425. ⟨10.1042/BJ20080952⟩. ⟨hal-00479024⟩