N-ras gene

Vasioukhin V> Anker P, Maurice P, Lyautey J, Lederrey C, Stroun M. Point mutations of the N Ras gene in the blood plasma DNA of patients with myelodys-plastic syndrome or acute myelogenous leukaemia. Br J Haematol 1994 86 774-9. 

Toxicity and effectivity studies have often been performed in rodent fibroblast cells containing oncogenic H-Ras. However, prenylation of K-Ras B and N-Ras are not as effectively blocked by the farnesyltransferase inhibitors as H-Ras [48] (see below). Thus normal cells may be less sensitive to these drugs because they express K-Ras 4B and N-Ras. In this context it should be noted that H-Ras mutations are relatively uncommon in human tumors [49]. Rather, the K-Ras gene is the most frequently mutated in solid human cancers, whereas N-Ras is prevalent in leukemias. Thus the preclinical evaluation of the farnesylation inhibitors has yet to be critically re-evaluated for trials in humans. 

Boissel, N., Leroy, H., Brethon, B., Philippe, N., de Botton, S., Auvrignon, A., Raffoirx, E., Leblanc, T., Thomas, X., Hermine, 0., et al. (2006) Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBE AML). 

Ras, a historical proto-oncogene, is frequently mutated in many human cancers, including 90% of pancreatic cancers, 50% of colorectal cancers, 30% of lung cancers, and 15-30% of melanomas [10-12]. There are three Ras genes that encode four family members K-Ras (two alternatively spliced isoforms), H-Ras, and N-Ras. Mutations are most commonly found in K-Ras [13]. These mutations result in impaired GTP hydrolysis, which shifts the equilibrium toward GTP-bound active Ras, and results in constitutive intracellular signaling. 

Jackson EL, Willis N, Mercer K et al (2001) Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev 15 3243-3248... 

Koizumi, M. and Ohtsuka, E. (1992) Design of RNAs that inhibit the activated c-Ha-ras gene in mammalian cells. Ann. N.Y. Acad. Sci., 660, 276. 

Ras genes are frequently mutated in chemically induced animal tumors and are the most frequently detected mutated oncogenes in human tumors. Approximately 20-30% of all human tumors contain mutated ras. The Ras subfamily includes H-ras, K-ras, and N-ra.v, and all have been found to be mutationally activated in numerous types of tumors from a large variety of species including humans. 

Hayashi I, Konishi N, Matsuda H, et al. 1996. Comparative analysis of pl6/CDKN2, p53 and ras gene alterations in human non-small cell lung cancers, with and without associated pulmonary asbestosis. Int J Oncol 8 85-90. 

Impaired GTPase activity in a regulatory protein also can lead to cancer. Indeed, ras is one of the genes most commonly mutated in human tumors. Mammalian cells contain three 21-kd Ras proteins (H-, K-, and N-Ras) that cycle between GTP and GDP forms. The most common mutations in tumors lead to a loss of the ability to hydrolyze GTP. Thus, the Ras protein is trapped in the "on" position and continues to stimulate cell growth. 

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