Gene array of VHL mutation and hypoxia shows novel hypoxia-induced genes and that cyclin D1 is a VHL target gene
| Autor: | Peter J. Ratcliffe, Edison T. Liu, Charles C. Wykoff, Patrick H. Maxwell, M E Cockman, Christos Sotiriou, Adrian L. Harris |
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| Rok vydání: | 2004 |
| Předmět: |
Carcinoma
Renal Cell -- genetics Cancer Research Ubiquitin-Protein Ligases Cyclin A cyclin D1 urologic and male genital diseases Tumor Suppressor Proteins -- genetics 03 medical and health sciences 0302 clinical medicine Cyclin D1 Downregulation and upregulation VHL Gene expression Tumor Cells Cultured medicine Kidney Neoplasms -- pathology Humans Kidney Neoplasms -- genetics Carcinoma Renal Cell -- pathology Carcinoma Renal Cell 030304 developmental biology hypoxia inducible factor1 0303 health sciences biology hypoxia Gene Expression Profiling Tumor Suppressor Proteins Genetics and Genomics Sciences bio-médicales et agricoles Hypoxia (medical) Cell cycle Molecular biology Cell Hypoxia Kidney Neoplasms 3. Good health Gene expression profiling Oncology Hypoxia-inducible factors Von Hippel-Lindau Tumor Suppressor Protein Ubiquitin-Protein Ligases -- genetics 030220 oncology & carcinogenesis Cancer research biology.protein Cyclin D1 -- pharmacology renal medicine.symptom |
| Zdroj: | British Journal of Cancer British Journal of Cancer, 90 (6 |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6601657 |
| Popis: | Gene expression analysis was performed on a human renal cancer cell line (786-0) with mutated VHL gene and a transfectant with wild-type VHL to analyse genes regulated by VHL and to compare with the gene programme regulated by hypoxia. There was a highly significant concordance of the global gene response to hypoxia and genes suppressed by VHL. Cyclin D1 was the most highly inducible transcript and 14-3-3 epsilon was downregulated. There were some genes regulated by VHL but not hypoxia in the renal cell line, suggesting a VHL role independent of hypoxia. However in nonrenal cell lines they were hypoxia regulated. These included several new pathways regulated by hypoxia, including RNase 6PL, collagen type 1 alpha 1, integrin alpha 5, ferritin light polypeptide, JM4 protein, transgelin and L1 cell adhesion molecule. These were not found in a recent SAGE analysis of the same cell line. Hypoxia induced downregulation of Cyclin D1 in nonrenal cells via an HIF independent pathway. The selective regulation of Cyclin D1 by hypoxia in renal cells may therefore contribute to the tissue selectivity of VHL mutation. Journal Article Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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