Gene expression profiling of hypoxia signaling in human hepatocellular carcinoma cells
| Autor: | Ajith Vengellur, John B. Hogenesch, John J. LaPres, J. M. Phillips |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Carcinoma
Hepatocellular Erythrocytes Transcription Genetic Physiology Angiogenesis Cell Oligonucleotides Down-Regulation Oxidative phosphorylation Deferoxamine Biology chemistry.chemical_compound Downregulation and upregulation Nickel Cell Line Tumor Genetics medicine Humans Hypoxia Glyceraldehyde 3-phosphate dehydrogenase DNA Primers Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Liver Neoplasms Nucleic Acid Hybridization Cobalt Hypoxia (medical) Up-Regulation Cell biology Gene Expression Regulation Neoplastic Oxygen Vascular endothelial growth factor medicine.anatomical_structure chemistry biology.protein RNA medicine.symptom Algorithms Pyruvate kinase Signal Transduction |
| Zdroj: | Physiological Genomics. 22:308-318 |
| ISSN: | 1531-2267 1094-8341 |
| Popis: | Cellular, local, and organismal responses to low O2availability occur during processes such as anaerobic metabolism and wound healing and pathological conditions such as stroke and cancer. These responses include increases in glycolytic activity, vascularization, breathing, and red blood cell production. These responses are mediated in part by the hypoxia-inducible factors (HIFs), which receive information on O2levels from a group of iron- and O2-dependent hydroxylases. Hypoxia mimics, such as cobalt chloride, nickel chloride, and deferoxamine, act to simulate hypoxia by altering the iron status of these hydroxylases. To determine whether these mimics are appropriate substitutes for the lower O2tension evoked naturally, we compared transcriptional responses of a Hep3B cell line using high-density oligonucleotide arrays. A battery of core genes was identified that was shared by all four treatments (hypoxia, cobalt, nickel, and deferoxamine) including glycolytic enzymes, cell cycle regulators, and apoptotic genes. Importantly, cobalt, nickel, and deferoxamine influenced transcription of distinct sets of genes that were not affected by cellular hypoxia. These global responses to hypoxia indicate a balancing act between adaptation and programmed cell death and suggest caution in the use of hypoxia mimics as substitutes for the low O2tension that occurs in vivo. |
| Databáze: | OpenAIRE |
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