The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CA9  -  carbonic anhydrase IX

Homo sapiens

Synonyms: CA-IX, CAIX, Carbonate dehydratase IX, Carbonic anhydrase 9, Carbonic anhydrase IX, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CA9


High impact information on CA9

  • For this purpose, a CTL line specific for the homologous segment of the envelope from the MN isolate of HIV-1 and restricted by the same class I major histocompatibility (MHC) molecule (Dd) as the IIIB-specific CTLs was raised from mice immunized with MN-env-recombinant vaccinia virus [5].
  • BACKGROUND & AIMS: CA IX (formerly MN protein) is a carbonic anhydrase isoenzyme whose expression is associated with human tumors [6].
  • Western blotting and immunohistochemical analyses of human and animal tissues were performed using CA IX-specific monoclonal antibody and rabbit antiserum to human CA II [6].
  • METHODS: A CA9 cDNA isolated from a human stomach library was sequenced along with the cDNA derived from HeLa cells [6].
  • Evolutionary conservation in vertebrates as well as abundant expression of CA IX protein in normal human gastric mucosa, but not in derived tumors, indicate its physiological importance [6].

Chemical compound and disease context of CA9


Biological context of CA9


Anatomical context of CA9


Associations of CA9 with chemical compounds

  • Percentage of expression was scored as well as colocalization of pimonidazole with CA IX [17].
  • The expression of CA IX on the luminal surface justifies investigation of its utility as a therapeutic target/prognostic indicator [18].
  • We found that both hypoxia-induced transcription and CA IX protein level are further increased by reduced glucose or bicarbonate concentrations [7].
  • In addition, topiramate and zonisamide were observed to behave as weak hCA XII inhibitors, while zonisamide was an effective hCA IX inhibitor (K(I) of 5.1 nM) [19].
  • WX-G250 targets the G250 antigen, and PS-341 disrupts the 26S proteasome mediating the degradation of intracellular proteins [20].

Physical interactions of CA9


Regulatory relationships of CA9


Other interactions of CA9

  • A model outlining the quantitative relationship between p53, HIF-1alpha, and CAIX is presented [23].
  • Lowered oxygen tension induces expression of the hypoxia marker MN/carbonic anhydrase IX in the absence of hypoxia-inducible factor 1 alpha stabilization: a role for phosphatidylinositol 3'-kinase [26].
  • Plasma from 36 patients with primary tumor samples had VEGF (R&D Systems, MN) and d-dimer (American Diagnostica, Greenwich, CT) levels determined [27].
  • Expression of a dominant-negative mutant of ERK2 reduced the CA9 promoter activity in both standard and acidic conditions [21].
  • METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA IX, CA XII and pVHL [15].

Analytical, diagnostic and therapeutic context of CA9

  • Using Northern blot analysis and immunostaining with specific antibodies we analyzed the expression of CA9 and CA12 genes and their products in a large sample of cancer cell lines, fresh and archival tumor specimens, and normal human tissues [14].
  • Tumors with a positive hypoxic profile (defined as high expression of both HIF-1alpha and CA9) were associated with worse progression-free survival (P = 0.04) [28].
  • METHODS: The expression of VEGF-A and CA9 was assessed in 5067 fresh frozen human tissue samples and 238 cell lines by DNA microarray analysis [29].
  • There was no difference in CAIX (p = 0.25), TGF-beta1 (p = 0.66) or bFGF (p = 0.18) between affected and control groups [30].
  • These data are critical for the design of novel antitumor therapies, mainly for hypoxic tumors that overexpress CA IX, which are nonresponsive to radiation or chemotherapy [31].


  1. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Wykoff, C.C., Beasley, N.J., Watson, P.H., Turner, K.J., Pastorek, J., Sibtain, A., Wilson, G.D., Turley, H., Talks, K.L., Maxwell, P.H., Pugh, C.W., Ratcliffe, P.J., Harris, A.L. Cancer Res. (2000) [Pubmed]
  2. Carbonic anhydrase XII is a marker of good prognosis in invasive breast carcinoma. Watson, P.H., Chia, S.K., Wykoff, C.C., Han, C., Leek, R.D., Sly, W.S., Gatter, K.C., Ratcliffe, P., Harris, A.L. Br. J. Cancer (2003) [Pubmed]
  3. Expression of hypoxia-related tissue factors in astrocytic gliomas. A multivariate survival study with emphasis upon carbonic anhydrase IX. Korkolopoulou, P., Perdiki, M., Thymara, I., Boviatsis, E., Agrogiannis, G., Kotsiakis, X., Angelidakis, D., Rologis, D., Diamantopoulou, K., Thomas-Tsagli, E., Kaklamanis, L., Gatter, K., Patsouris, E. Hum. Pathol. (2007) [Pubmed]
  4. Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1alpha-related markers, and hemoglobin levels. Bache, M., Reddemann, R., Said, H.M., Holzhausen, H.J., Taubert, H., Becker, A., Kuhnt, T., H??nsgen, G., Dunst, J., Vordermark, D. Int. J. Radiat. Oncol. Biol. Phys. (2006) [Pubmed]
  5. A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. Takahashi, H., Merli, S., Putney, S.D., Houghten, R., Moss, B., Germain, R.N., Berzofsky, J.A. Science (1989) [Pubmed]
  6. Carbonic anhydrase IX, MN/CA IX: analysis of stomach complementary DNA sequence and expression in human and rat alimentary tracts. Pastoreková, S., Parkkila, S., Parkkila, A.K., Opavský, R., Zelník, V., Saarnio, J., Pastorek, J. Gastroenterology (1997) [Pubmed]
  7. Induction by hypoxia combined with low glucose or low bicarbonate and high posttranslational stability upon reoxygenation contribute to carbonic anhydrase IX expression in cancer cells. Rafajová, M., Zatovicová, M., Kettmann, R., Pastorek, J., Pastoreková, S. Int. J. Oncol. (2004) [Pubmed]
  8. Immunohistochemical study of colorectal tumors for expression of a novel transmembrane carbonic anhydrase, MN/CA IX, with potential value as a marker of cell proliferation. Saarnio, J., Parkkila, S., Parkkila, A.K., Haukipuro, K., Pastoreková, S., Pastorek, J., Kairaluoma, M.I., Karttunen, T.J. Am. J. Pathol. (1998) [Pubmed]
  9. Distinct patterns of hypoxic expression of carbonic anhydrase IX (CA IX) in human malignant glioma cell lines. Said, H.M., Staab, A., Hagemann, C., Vince, G.H., Katzer, A., Flentje, M., Vordermark, D. J. Neurooncol. (2007) [Pubmed]
  10. Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment. Pastorek, J., Pastoreková, S., Callebaut, I., Mornon, J.P., Zelník, V., Opavský, R., Zat'ovicová, M., Liao, S., Portetelle, D., Stanbridge, E.J. Oncogene (1994) [Pubmed]
  11. Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes. Ivanov, S.V., Kuzmin, I., Wei, M.H., Pack, S., Geil, L., Johnson, B.E., Stanbridge, E.J., Lerman, M.I. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  12. Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships. Opavský, R., Pastoreková, S., Zelník, V., Gibadulinová, A., Stanbridge, E.J., Závada, J., Kettmann, R., Pastorek, J. Genomics (1996) [Pubmed]
  13. Effects of von Hippel-Lindau gene mutation and methylation status on expression of transmembrane carbonic anhydrases in renal cell carcinoma. Ashida, S., Nishimori, I., Tanimura, M., Onishi, S., Shuin, T. J. Cancer Res. Clin. Oncol. (2002) [Pubmed]
  14. Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. Ivanov, S., Liao, S.Y., Ivanova, A., Danilkovitch-Miagkova, A., Tarasova, N., Weirich, G., Merrill, M.J., Proescholdt, M.A., Oldfield, E.H., Lee, J., Zavada, J., Waheed, A., Sly, W., Lerman, M.I., Stanbridge, E.J. Am. J. Pathol. (2001) [Pubmed]
  15. Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa. Kivela, A.J., Parkkila, S., Saarnio, J., Karttunen, T.J., Kivela, J., Parkkila, A.K., Bartosova, M., Mucha, V., Novak, M., Waheed, A., Sly, W.S., Rajaniemi, H., Pastorekova, S., Pastorek, J. World J. Gastroenterol. (2005) [Pubmed]
  16. Expression of hypoxia-inducible factor 1 alpha and its downstream targets in fibroepithelial tumors of the breast. Kuijper, A., van der Groep, P., van der Wall, E., van Diest, P.J. Breast Cancer Res. (2005) [Pubmed]
  17. Hypoxia in human colorectal adenocarcinoma: Comparison between extrinsic and potential intrinsic hypoxia markers. Goethals, L., Debucquoy, A., Perneel, C., Geboes, K., Ectors, N., De Schutter, H., Penninckx, F., McBride, W.H., Begg, A.C., Haustermans, K.M. Int. J. Radiat. Oncol. Biol. Phys. (2006) [Pubmed]
  18. The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer. Turner, K.J., Crew, J.P., Wykoff, C.C., Watson, P.H., Poulsom, R., Pastorek, J., Ratcliffe, P.J., Cranston, D., Harris, A.L. Br. J. Cancer (2002) [Pubmed]
  19. Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. Nishimori, I., Vullo, D., Innocenti, A., Scozzafava, A., Mastrolorenzo, A., Supuran, C.T. Bioorg. Med. Chem. Lett. (2005) [Pubmed]
  20. Targeted agents for the treatment of advanced renal cell carcinoma. Staehler, M., Rohrmann, K., Haseke, N., Stief, C.G., Siebels, M. Current drug targets. (2005) [Pubmed]
  21. Extracellular acidosis elevates carbonic anhydrase IX in human glioblastoma cells via transcriptional modulation that does not depend on hypoxia. Ihnatko, R., Kubes, M., Takacova, M., Sedlakova, O., Sedlak, J., Pastorek, J., Kopacek, J., Pastorekova, S. Int. J. Oncol. (2006) [Pubmed]
  22. Carbonic anhydrase IX reduces E-cadherin-mediated adhesion of MDCK cells via interaction with beta-catenin. Svastová, E., Zilka, N., Zat'ovicová, M., Gibadulinová, A., Ciampor, F., Pastorek, J., Pastoreková, S. Exp. Cell Res. (2003) [Pubmed]
  23. DNA damage is a prerequisite for p53-mediated proteasomal degradation of HIF-1alpha in hypoxic cells and downregulation of the hypoxia marker carbonic anhydrase IX. Kaluzová, M., Kaluz, S., Lerman, M.I., Stanbridge, E.J. Mol. Cell. Biol. (2004) [Pubmed]
  24. MAPK pathway contributes to density- and hypoxia-induced expression of the tumor-associated carbonic anhydrase IX. Kopacek, J., Barathova, M., Dequiedt, F., Sepelakova, J., Kettmann, R., Pastorek, J., Pastorekova, S. Biochim. Biophys. Acta (2005) [Pubmed]
  25. Tumor-associated carbonic anhydrases and their clinical significance. Pastorekova, S., Parkkila, S., Zavada, J. Advances in clinical chemistry (2006) [Pubmed]
  26. Lowered oxygen tension induces expression of the hypoxia marker MN/carbonic anhydrase IX in the absence of hypoxia-inducible factor 1 alpha stabilization: a role for phosphatidylinositol 3'-kinase. Kaluz, S., Kaluzová, M., Chrastina, A., Olive, P.L., Pastoreková, S., Pastorek, J., Lerman, M.I., Stanbridge, E.J. Cancer Res. (2002) [Pubmed]
  27. HER-2 gene amplification correlates with higher levels of angiogenesis and lower levels of hypoxia in primary breast tumors. Blackwell, K.L., Dewhirst, M.W., Liotcheva, V., Snyder, S., Broadwater, G., Bentley, R., Lal, A., Riggins, G., Anderson, S., Vredenburgh, J., Proia, A., Harris, L.N. Clin. Cancer Res. (2004) [Pubmed]
  28. Coexpression of hypoxia-inducible factors 1alpha and 2alpha, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival. Hui, E.P., Chan, A.T., Pezzella, F., Turley, H., To, K.F., Poon, T.C., Zee, B., Mo, F., Teo, P.M., Huang, D.P., Gatter, K.C., Johnson, P.J., Harris, A.L. Clin. Cancer Res. (2002) [Pubmed]
  29. Expression of vascular endothelial growth factor, hypoxia inducible factor 1alpha, and carbonic anhydrase IX in human tumours. Jubb, A.M., Pham, T.Q., Hanby, A.M., Frantz, G.D., Peale, F.V., Wu, T.D., Koeppen, H.W., Hillan, K.J. J. Clin. Pathol. (2004) [Pubmed]
  30. Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of digital clubbing. Atkinson, S., Fox, S.B. J. Pathol. (2004) [Pubmed]
  31. Carbonic anhydrase inhibitors: inhibition of transmembrane, tumor-associated isozyme IX, and cytosolic isozymes I and II with aliphatic sulfamates. Winum, J.Y., Vullo, D., Casini, A., Montero, J.L., Scozzafava, A., Supuran, C.T. J. Med. Chem. (2003) [Pubmed]
WikiGenes - Universities