title: Distinct patterns of hypoxic expression of carbonic anhydrase IX (CA IX) in human malignant glioma cell lines.
abstract: The hypoxia-inducible enzyme carbonic anhydrase IX (CA IX) has recently been discussed as a surrogate marker of tumor hypoxia, an indicator of prognosis and a potential therapeutic target in malignant glioma. To characterize patterns of expression of CA IX in human malignant glioma cells, we studied CA IX protein, CA9 mRNA and hypoxia-inducible factor-1alpha (HIF-1alpha) protein levels in U87-MG, U251, U373 and GaMG cells exposed to in vitro hypoxia (1, 6 or 24 h at 5%, 1% or 0.1% O(2)). All cell lines displayed a strong hypoxic induction of CA9 mRNA in response to prolonged severe hypoxia with cell-line specific patterns at moderate to mild hypoxia and shorter treatment times. Only U87-MG exhibited a strong constitutive, normoxic expression of CA IX protein without a detectable change under hypoxia. In U251 and GaMG cell lines, a marked induction of CA IX protein in response to severe hypoxia was seen. CA IX changes under severe hypoxia and the inhibitory effect of the glycolysis inhibitor iodoacetate (IAA, 50 microM) on hypoxic CA IX overexpression were paralleled by the results for HIF-1alpha protein. Therefore, immunohistochemical CA IX staining in human malignant glioma specimens can result from low oxygen concentrations or constitutive, oncogene-related, overexpression both of which may be prognostically relevant.
authors.affiliation: Department of Radiation Oncology, University of Wuerzburg, Josef-Schneider-Strasse 11, 97080 Wuerzburg, Germany. Said_h@klinik.uni-wuerzburg.de
authors.forename: Harun M
authors.initials: HM
authors.lastname: Said
authors.forename: Adrian
authors.initials: A
authors.lastname: Staab
authors.forename: Carsten
authors.initials: C
authors.lastname: Hagemann
authors.forename: Giles H
authors.initials: GH
authors.lastname: Vince
authors.forename: Astrid
authors.initials: A
authors.lastname: Katzer
authors.forename: Michael
authors.initials: M
authors.lastname: Flentje
authors.forename: Dirk
authors.initials: D
authors.lastname: Vordermark
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000201:enzymology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007527:Isoenzymes; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D012333:RNA, Messenger; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases