Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bloethner, S; Chen, B; Hemminki, K; Müller-Berghaus, J; Ugurel, S; Schadendorf, D; Kumar, R.
Effect of common B-RAF and N-RAS mutations on global gene expression in melanoma cell lines.
Carcinogenesis. 2005; 26(7):1224-1232
Doi: 10.1093/carcin/bgi066
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- Co-Autor*innen der Med Uni Graz
- Ugurel-Becker Selma
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- Abstract:
- We studied global gene expression in three melanoma cell lines with the most common and potent V600E mutation in the B-RAF gene-four cell lines with a common Q61R mutation in the N-RAS gene and three cell lines with no mutations using human HG-U133A 2.0 micro-arrays with 22 277 transcripts. Data analysis using stringent criteria revealed several upregulated and downregulated genes in cell lines with B-RAF and N-RAS mutations compared with cell lines without mutations. We found 29 genes specifically upregulated and 32 genes downregulated in cell lines with B-RAF mutations, whereas 70 genes were upregulated and 39 downregulated in cell lines with N-RAS mutations; 11 genes showed overlapping upregulation and 45 downregulation. The micro-array data for nine selected genes were validated by the real-time PCR technique. Expression of a large number of genes, that encode members or regulators of the RAS/RAF/MEK/ERK pathways or are involved in metastasis or invasion, was affected in cell lines with mutations in B-RAF and N-RAS. Upregulated genes in cell lines with mutations included dual-specificity phosphatase 6 (DUSP6), sprouty 2 (SPRY2), v-akt murine thymoma viral oncogene homolog 3 (AKT3) and matrix metalloproteinase 14 (MMP14); downregulated genes included interleukin 18 (IL18), Krüppel-like factor 5 (KLF5) and inhibitor of DNA binding 2 (ID2). Our results, though carried on cell lines, provide a novel insight into the effect of mutations in the B-RAF and N-RAS genes on global gene expression in melanoma and highlight the complexity of mechanisms involved in tumour initiation and maintenance.
- Find related publications in this database (using NLM MeSH Indexing)
- DNA Mutational Analysis -
- Down-Regulation -
- Gene Expression Profiling -
- Genes, ras - genetics
- Humans -
- Melanoma - genetics
- Oligonucleotide Array Sequence Analysis -
- Polymerase Chain Reaction -
- Proto-Oncogene Proteins B-raf - genetics
- Skin Neoplasms - genetics
- Tumor Cells, Cultured -
- Up-Regulation -