Src induces expression of carbonic anhydrase IX via hypoxia-inducible factor 1.

Carbonic anhydrase IX (CA IX) belongs to the physiologically important enzymes which contribute to tumor physiology. Tumor-associated expression of CA IX is induced mainly due to its strong transcriptional activation via hypoxia-inducible factor 1 (HIF-1). Therefore, CA IX can serve as a surrogate marker of hypoxia and a prognostic indicator.

Role of the HBx oncoprotein in carbonic anhydrase 9 induction.

Carbonic anhydrase 9 (CA9), as one of the most hypoxia-responsive genes, has been associated almost exclusively with hypoxic tumors. Its principal role is in pH regulation which helps tumor cells overcome intracellular acidosis and survive extended periods of time with low oxygen. Hypoxia-inducible factor 1 (HIF-1) is the main transcriptional activator of CA9.

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

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.

Type 1 and 2 IP3 receptors respond differently to catecholamines and stress.

Type 1 and 2 inositol 1,4,5-trisphosphate (IP3) receptors have been found in cardiac tissue, although they are localized in different types of cells. While the type 1 predominates in neuronal cells and cardiac ganglia, type 2 IP3 receptor is localized mainly in cardiomyocytes. In the heart, gene expression of the type 1 IP3 receptor is modulated by catecholamines, while type 2 is not affected.

Hypoxia upregulates expression of human endosialin gene via hypoxia-inducible factor 2.

Endosialin is a transmembrane glycoprotein selectively expressed in blood vessels and stromal fibroblasts of various human tumours. It has been functionally implicated in angiogenesis, but the factors that control its expression have remained unclear. As insufficient delivery of oxygen is a driving force of angiogenesis in growing tumours, we investigated whether hypoxia regulates endosialin expression.

Induction of carbonic anhydrase IX by hypoxia and chemical disruption of oxygen sensing in rat fibroblasts and cardiomyocytes.

CA IX is an active transmembrane carbonic anhydrase isoform functionally implicated in cell adhesion and pH control. Human CA IX is strongly induced by hypoxia and frequently associated with various tumors. In this study, we investigated the expression of the rat CA IX in response to chronic hypoxia and to treatment with chemical compounds that disrupt oxygen sensing, including dimethyloxalylglycine, dimethylester succinate, diazoxide, and tempol.

Alternative splicing variant of the hypoxia marker carbonic anhydrase IX expressed independently of hypoxia and tumour phenotype.

CA IX is a hypoxia-induced, cancer-associated carbonic anhydrase isoform with functional involvement in pH control and cell adhesion. Here we describe an alternative splicing variant of the CA9 mRNA, which does not contain exons 8-9 and is expressed in tumour cells independently of hypoxia. It is also detectable in normal tissues in the absence of the full-length transcript and can therefore produce false-positive data in prognostic studies based on the detection of the hypoxia- and cancer-related CA9 expression.