Thus it seems that the ability of ras to trigger

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Unformatted text preview: bility of RAS to trigger either growth or apoptosis depends on the balance of interactions between pro-growth, pro-survival and pro-death effectors (24). Oncogenic RAS and human cancer As mentioned above, RAS genes are among the most frequently mutated genes in human cancers, but different malignancies display different frequencies and spectra of mutations in NRAS, HRAS, and KRAS. The important role of RAS in the regulation of cell growth and differentiation is verified by the fact that approximately 35% of neoplasias display mutations in this gene family, especially in the codons 12, 13, 59 and 61. In vivo mutations in RAS genes are not equally distributed between the RAS isoforms in different malignancies. The KRAS gene is mutated in nonsmall cell lung cancer (33%), colorectal cancer (44%), and pancreas cancer (90%), liver cancer (30%), and acute myelogenous leukemia (30%); HRAS gene is mutated in bladder cancer (10%), while kidney cancer (10%) and thyroid carcinomas have mutations in all three RAS genes (24). NRAS is the most frequently mutated gene in a wide variety of human leukaemias with an incidence of up to 60% in chronic myelomonocytic leukaemia and up to 40% in acute myelogenous leukaemia (101). Mutations of codon 61 of NRAS in thyroid follicular tumors occurred in 23% and 18% of atypical adenomas and follicular carcinomas, respectively. NRAS mutations was also found in liver 30% of cancer (OMIM:http://www.n 24 Targeting the RAS oncogenes RAS proteins are intracellular key transducers of growth signals regulated by cell surface receptors. Since a high percentage of human tumors harbor oncogenic RAS mutants this oncoprotein could be an appropriate target for drug design. The major anti-RAS therapy approaches, at present, include the prevention of RAS membrane localization by farnesyltransferase inhibitors (102), and inhibition of RAS protein expression by antisense oligonucleotides, and RNA interference (RNAi) (16, 103, 104). Farnesylation of RAS is esse...
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This document was uploaded on 03/06/2014.

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