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Byline: P. B. Kopnin (1,2), A. V. Ivanov (1), G. V. Il'inskaya (3), A. A. Sablina (3), B. P. Kopnin (3), P. M. Chumakov (1) Keywords: cell cycle; neoplastic transformation; RAS; p53 Abstract: A study was made of the effect of activated oncogene N-RAS on the function of tumor suppressor p53 and the proliferating ability of rat embryo fibroblasts REF52. The proliferation rate and the portion of S-phase cells increased in the first three days of N-RAS expression. After 5--7 days, the p53 function was enhanced, as manifest in increased p53 lifespan and nuclear content and induced transcription of p53-responsive genes. In particular, p21.sup.WAF1/CIP1, an inhibitor of cyclin-dependent kinase 2, was produced to a higher level and arrested the cell cycle in G1. Cells with abrogated or dramatically inhibited N-RAS expression were generated at this stage. Having a selective advantage, these cells gradually displaced N-RAS-expressing cells arrested in G1, so that one month after oncogene induction the culture mostly consisted of morphologically normal, actively proliferating Ras-negative cells. Neither cell cycle arrest nor reversion to the normal phenotype were observed in N-RAS expressing cells devoid of the p53 function. Thus, p53 prevented stable N-RAS-induced transformation of REF52 cells, arresting the cell cycle and expediting revertant selection. Author Affiliation: (1) Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia (2) Moscow Center of Medical Research, University of Oslo, Moscow, 117334, Russia (3) Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia Article History: Registration Date: 12/10/2004