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Oncogenic NRAS has multiple effects on the malignant phenotype of human melanoma cells cultured in vitro
Author(s) -
Eskandarpour Malihe,
Huang Fei,
Reeves Karen A.,
Clark Edwin,
Hansson Johan
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23876
Subject(s) - neuroblastoma ras viral oncogene homolog , cancer research , downregulation and upregulation , urokinase receptor , biology , melanoma , gene knockdown , cell growth , microphthalmia associated transcription factor , microbiology and biotechnology , gene , kras , mutation , cell , genetics , transcription factor
Activating mutations in the NRAS gene, which occur predominantly in codon 61 (Q61R, Q61K) are among the most common genetic events in malignant melanoma. NRAS protein with oncogenic codon 61 mutations may therefore be good therapeutic targets. In the present study, we used gene expression profiling as a method for global characterization of gene expression alterations that resulted from treatment of melanoma cells with siRNA specifically targeting NRAS Q61R . Sixteen probe sets representing 15 unique genes were identified whose expression was significantly altered by siRNA against NRAS Q61R in 2 melanoma cell lines. The genes with altered expression are involved in several functions, including modulation of cell growth, invasion and migration. The results suggest that downregulation of cyclin E2 and cyclin D1 and also upregulation of the negative cell‐cycle regulator HBP1 in NRAS Q61R knockdown cells contribute to the inhibition of cell proliferation. Furthermore, suppression of oncogenic NRAS results in reduced migration and invasion, which is accompanied by downregulation of EphA2 (a receptor tyrosine kinase), uPAR (urokinase receptor) and cytoskeleton proteins such as leupaxin, paxillin and vinculin. These studies support the concept that suppression of oncogenic NRAS by siRNA can induce growth arrest and inhibit invasion of human melanoma cells by modulating the levels of these gene products. © 2008 Wiley‐Liss, Inc.