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Carbonic Anhydrase IX and Hypoxic Response: A Path to Tumors

Wednesday, November 30th, 2011

Carbonic Anhydrase IX (CA-IX) is an enzyme that is induced under hypoxic conditions. This enzyme is rarely present in normal cells and is responsible for controlling tumor pH. CA-IX is a transmembrane glycoprotein of the zinc metalloenzyme family. This family displays 15 isoforms in human tissues. Carbonic Anhydrase IX functions to convert carbonic acid present in hypoxic cells into a biocarbonate and a proton. Due to the hypoxic conditions found in many tumors CA-IX has become a marker of hypoxia and expression has been associated with several tumors such as lung, brain, colorectal, ovarian, renal, breast, and cervical to name a few.

Western Blot: Carbonic Anhydrase IX Antibody

Carbonic Anhydrase IX can be regulated through Hypoxia Inducible Factors. HIF proteins cause upregulation of the CA-IX gene to stabilize the microenvironment of tumor/hypoxic cells. The upregulation of the CA-IX gene is caused by Hypoxia Inducible Factor (HIF) undergoing specific hydroxylations dependent on oxygen conditions within the cell. Once the hydroxylation occurs HIF-1 alpha can interact with the beta domain on the Von Hippel-Lindau protein. In the presence of oxygen, HIF proteins will undergo rapid degradation. In the absence of oxygen, HIF can activate a signal cascade to transcribe several targets such as Carbonic Anhydrase IX. Since many tumors induce hypoxic conditions, CA-IX is being used as a marker. Studies are being performed to look at levels of hypoxia within certain tumors, as hypoxic tumors often are more aggressive and have a lower survival rate. Tan, E. Y., et al. [PMID: 19165203] suggested that CA-IX positive tumors may be due to an advanced hypoxic response and that continued research on the HIF pathway and targets regulated by this pathway such as CA-IX are pivotal in future cancer research.

Novus Biologicals offers CA-IX reagents for your research needs including: