Artikel
Comparative analysis of hypoxia regulated tumour marker gene(s) in human tumors and tumor cell lines
Untersuchung der Hypoxie-regulierten Tumormarkergen(e) in humanen Tumoren und Tumor-Zelllinien
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Autoren
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H.M. Said
- Department of Radiation Oncology, University of Wuerzburg
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C. Hagemann
- Department of Neurosurgery, Tumorbiology Laboratory; University of Wuerzburg
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C. Vollmuth
- Department of Neurosurgery, Tumorbiology Laboratory; University of Wuerzburg
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J. Stojic
- Department of Neurosurgery, Tumorbiology Laboratory; University of Wuerzburg
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G.H. Vince
- Department of Neurosurgery, Tumorbiology Laboratory; University of Wuerzburg
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D. Vordermark
- Department of Radiation Oncology, University of Wuerzburg
| Veröffentlicht: | 8. Mai 2006 |
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Gliederung
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Objective: The ability to adapt to environmental changes is essential for an organism's survival. Normal cells exposed to transient or moderate hypoxia are generally able to adapt to the hypoxic conditions largely through activation of the hypoxia-inducible transcription factor HIF1α and its successive regulatory function. Induction of HIF-1α target genes, in solid tumors, can promote disease. Carbonic anhydrase IX (CA-IX) is a HIF-1α-regulated endogenenous hypoxia marker. It is expressed in response to hypoxic conditions in tumour cells. The correlation between tumour hypoxia and expression of genes like CA-IX in human glioma was not examined intensively.
Methods: Total RNA was extracted from different human tumor tissue(s). Expression of HIF-1α-regulating genes or HIF-1α-regulated genes in these tumors was examined by analysing these RNAs via semi-quantitative RT-PCR. In a parallel approach, human U251, U87-MG, U373 an GaMG glioma monolayer cell cultures were cultivated and treated in an Invivo2-200 Ruskinn hypoxia incubator for 1 h, 6 h, 24 h with 5%, 1% or 0.1% O2, in addition to 24 h with re-oxygenation for 24 or 48 h. Normoxic conditions were (20% O2, 5% CO2). Total RNA was extracted from these hypoxia exposed cultured cell lines and the expression of these genes was monitored via semi quantitative RT PCR. β-actin and GAPDH served as housekeeping genes.
Results: The various human brain tumors and the human glioma cell lines cultivated under different aeration conditions displayed different level(s) of expression for hypoxia induced HIF-1α-regulated gene(s) like CA-IX or HIF-1α-regulating gene(s). CA-IX showed an O2 dependent expression pattern.
Conclusions: Hypoxia induced gene(s) or the genes regulating theses gene(s) in human brain tumors (in-vivo) or human glioma cells show (in-vitro) different patterns of normoxic and hypoxic expression of HIF-1α-regulated hypoxia induced genes like CA-IX. The examination of other HIF-1α-regulated genes or HIF-1α-regulating gene(s) will give new insights into the molecular mechanisms that regulate the oxygen-sensitivity of HIF-1α.
