Carcinogenesis Advance Access published online on March 10, 2005
Carcinogenesis, doi:10.1093/carcin/bgi066
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
* To whom correspondence should be addressed. 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 up-regulated and down-regulated genes in cell lines with B-RAF and N-RAS mutations compared to cell lines without mutations. We found 29 genes specifically up-regulated and 32 genes down-regulated in cell lines with B-RAF mutations, whereas 70 genes were up-regulated and 39 down-regulated in cell lines with N-RAS mutations; 11 genes showed overlapping up-regulation and 45 down-regulation. The micro-array data for nine selected genes were validated with real-time PCR. 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. Up-regulated 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); down-regulated 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 NRAS genes on global gene expression in melanoma and highlight the complexity of mechanisms involved in tumour initiation and maintenance.
Received December 6, 2004
Revised January 28, 2005
Accepted February 26, 2005
CANCER BIOLOGY
Effect of common B-RAF and N-RAS mutations on global gene expression in melanoma cell lines
2 Division of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany; Department of Biosciences, Karolinska Institute, 141 57 Huddinge, Sweden
3 Skin Cancer Unit, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Rajiv Kumar, E-mail: r.kumar{at}dkfz.de
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Edwin, K. Anderson, C. Ying, and T. B. Patel Intermolecular Interactions of Sprouty Proteins and Their Implications in Development and Disease Mol. Pharmacol., October 1, 2009; 76(4): 679 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Brady, M. L. Coleman, J. Munro, S. M. Feller, N. A. Morrice, and M. F. Olson Sprouty2 Association with B-Raf Is Regulated by Phosphorylation and Kinase Conformation Cancer Res., September 1, 2009; 69(17): 6773 - 6781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Pratilas, B. S. Taylor, Q. Ye, A. Viale, C. Sander, D. B. Solit, and N. Rosen V600EBRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway PNAS, March 17, 2009; 106(11): 4519 - 4524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Anglesio, J. M. Arnold, J. George, A. V. Tinker, R. Tothill, N. Waddell, L. Simms, B. Locandro, S. Fereday, N. Traficante, et al. Mutation of ERBB2 Provides a Novel Alternative Mechanism for the Ubiquitous Activation of RAS-MAPK in Ovarian Serous Low Malignant Potential Tumors Mol. Cancer Res., November 1, 2008; 6(11): 1678 - 1690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lito, B. D. Mets, S. Kleff, S. O'Reilly, V. M. Maher, and J. J. McCormick Evidence That Sprouty 2 Is Necessary for Sarcoma Formation by H-Ras Oncogene-transformed Human Fibroblasts J. Biol. Chem., January 25, 2008; 283(4): 2002 - 2009. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Oliveira, N. Bidere, J. E. Niemela, L. Zheng, K. Sakai, C. P. Nix, R. L. Danner, J. Barb, P. J. Munson, J. M. Puck, et al. NRAS mutation causes a human autoimmune lymphoproliferative syndrome PNAS, May 22, 2007; 104(21): 8953 - 8958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Shields, N. E. Thomas, M. Cregger, A. J. Berger, M. Leslie, C. Torrice, H. Hao, S. Penland, J. Arbiser, G. Scott, et al. Lack of Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Signaling Shows a New Type of Melanoma Cancer Res., February 15, 2007; 67(4): 1502 - 1512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kono, I. S. Dunn, P. J. Durda, D. Butera, L. B. Rose, T. J. Haggerty, E. M. Benson, and J. T. Kurnick Role of the Mitogen-Activated Protein Kinase Signaling Pathway in the Regulation of Human Melanocytic Antigen Expression Mol. Cancer Res., October 1, 2006; 4(10): 779 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Fritzsche, M Kenzelmann, M J Hoffmann, M Muller, R Engers, H-J Grone, and W A Schulz Concomitant down-regulation of SPRY1 and SPRY2 in prostate carcinoma. Endocr. Relat. Cancer, September 1, 2006; 13(3): 839 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Onken, J. P. Ehlers, L. A. Worley, J. Makita, Y. Yokota, and J. W. Harbour Functional Gene Expression Analysis Uncovers Phenotypic Switch in Aggressive Uveal Melanomas. Cancer Res., May 1, 2006; 66(9): 4602 - 4609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Ramnarain, S. Park, D. Y. Lee, K. J. Hatanpaa, S. O. Scoggin, H. Otu, T. A. Libermann, J. M. Raisanen, R. Ashfaq, E. T. Wong, et al. Differential Gene Expression Analysis Reveals Generation of an Autocrine Loop by a Mutant Epidermal Growth Factor Receptor in Glioma Cells Cancer Res., January 15, 2006; 66(2): 867 - 874. [Abstract] [Full Text] [PDF]
|
|