Effect of common B-RAF and N-RAS mutations on global gene expression in melanoma cell lines
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 ana...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
10 March 2005
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| In: |
Carcinogenesis
Year: 2005, Jahrgang: 26, Heft: 7, Pages: 1224-1232 |
| ISSN: | 1460-2180 |
| DOI: | 10.1093/carcin/bgi066 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/carcin/bgi066
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| Verfasserangaben: | Sandra Bloethner, Bowang Chen, Kari Hemminki, Jan Müller-Berghaus, Selma Ugurel, Dirk Schadendorf and Rajiv Kumar |
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| 520 | |a 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. | ||
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