Therefore to better define the role of this oncogene

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Unformatted text preview: lanomas. Therefore, to better define the role of this oncogene in melanoma development, we specifically targeted this mutant oncogene using RNAi techniques and studied the effect of suppression of mutant NRAS on melanoma cell lines. Suppression of oncogenic NRAS in these cell lines resulted in decreased proliferation, increased apoptosis as well as decreased phosphorylation of ERK and Akt, and also reduced expression of NF-κB and cyclin D1 downstream in the NRAS signaling pathway. To follow up this investigation, we studied the effect of siRNA against mutant NRAS on 3 gene expression profiles in melanoma cell lines which carry oncogenic NRAS mutations. We could show the impact of knockdown of the NRAS oncogene on different cellular processes. For instance, we observed a disability of cells with respect to migration and invasion, which is accompanied by down-regulation of EphA2, uPAR and cytoskeleton proteins such as leupaxin, α-actinin, paxillin, and vinculin. These cells also showed inhibition of cell proliferation accompanied by downregulation of two cyclins, cyclin D1, cyclin E2, and up-regulation of HBP1 repressor. In summary, we conclude that the use of siRNAs against NRASQ61R is an important tool in suppressing oncogenic NRAS signaling, which might contribute to the development of more specific melanoma therapy in the subset of patients with tumor with NRAS mutations. 4 Cutaneous malignant melanoma Cutaneous malignant melanoma (CMM) is a tumor derived from transformed genetically altered epidermal melanocytes in the skin, as a result of complex interactions between genetics, and environmental factors. Melanocytes, which are localized in the basal layer of the epidermis, synthesize and transfer melanin pigment to surrounding keratinocytes, thereby protecting these cells from harmful exposure to UV radiation (1). Melanoma is a most rapidly increasing malignancy. In some parts of the word, especially in Western countries with Caucasian populations, the number of new cases of melanoma each year is increasing faster than any other cancer...
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This document was uploaded on 03/06/2014.

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