GLUT-1 and CAIX as intrinsic markers of hypoxia in carcinoma of the cervix: relationship to pimonidazole binding.
The presence of hypoxia in tumours results in the overexpression of certain genes, which are controlled via the transcription factor HIF-1. Hypoxic cells are known to be radioresistant and chemoresistant, thus, a reliable surrogate marker of hypoxia is desirable to ensure that treatment may be rationally applied. Recently, the HIF-1-regulated proteins Glut-1 and CAIX were validated as intrinsic markers of hypoxia by comparison with pO(2) measured using oxygen electrodes. We compare the expression of Glut-1 and CAIX with the binding of the bioreductive drug hypoxia marker pimonidazole. Pimonidazole was administered to 42 patients with advanced carcinoma of the cervix, 16 hr before biopsy. Sections of single or multiple biopsies were then immunostained for Glut-1 and CAIX, and the area of staining scored by eye, using a "field-by-field" semi-quantitative averaging system. Using 1 biopsy only, Glut-1 (r = 0.54, p = <0.001) correlated with the level of pimonidazole binding, and Glut-1 and CAIX expression also correlated significantly (r = 0.40, p = <0.009). Thus, our study has shown that HIF-1 regulated genes have potential for future use as predictors of the malignant changes mediated by hypoxia, and warrant further investigation as indicators of response to cancer therapy.
Airley
Rachel E
RE
School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, United Kingdom. R.Airley@livjm.ac.uk
Loncaster
Juliette
J
Raleigh
James A
JA
Harris
Adrian L
AL
Davidson
Susan E
SE
Hunter
Robert D
RD
West
Catharine M L
CM
Stratford
Ian J
IJ
D000328:Adult; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D015415:Biomarkers; D001706:Biopsy; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008839:Microelectrodes; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009593:Nitroimidazoles / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D015588:Observer Variation; D010100:Oxygen / Q000032:analysis; D010313:Partial Pressure; D011838:Radiation-Sensitizing Agents / Q000378:metabolism*; D015203:Reproducibility of Results; D014157:Transcription Factors; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
D000951:Antigens, Neoplasm; D015415:Biomarkers; D004268:DNA-Binding Proteins; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009004:Monosaccharide Transport Proteins; D009363:Neoplasm Proteins; D009593:Nitroimidazoles; D009687:Nuclear Proteins; D011838:Radiation-Sensitizing Agents; C495677:SLC2A1 protein, human; D014157:Transcription Factors; C033815:pimonidazole; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D010100:Oxygen