Effect of common B-RAF and N-RAS mutations on global gene expression in melanoma cell lines

• Verfasst von: Blöthner, Sandra [VerfasserIn]
• Verfasst von: Chen, Bowang [VerfasserIn]
• Verfasst von: Hemminki, Kari [VerfasserIn]
• Verfasst von: Ugurel, Selma [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Verfasst von: Kumar, Rajiv [VerfasserIn]
• Titel: Effect of common B-RAF and N-RAS mutations on global gene expression in melanoma cell lines
• Verf.angabe: Sandra Bloethner, Bowang Chen, Kari Hemminki, Jan Müller-Berghaus, Selma Ugurel, Dirk Schadendorf and Rajiv Kumar
• E-Jahr: 2005
• Jahr: 10 March 2005
• Umfang: 9 S.
• Fussnoten: Gesehen am 05.02.2021
• Titel Quelle: Enthalten in: Carcinogenesis
• Ort Quelle: Oxford : Oxford Univ. Press, 1980
• Jahr Quelle: 2005
• Band/Heft Quelle: 26(2005), 7, Seite 1224-1232
• ISSN Quelle: 1460-2180
• DOI: doi:10.1093/carcin/bgi066
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1747460508

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.