title: [The protective role of p53 in Ras-induced transformation of REF52 cells].
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, Cdk2 p21WAF1/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 Res-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.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow Center of Medical Research, University of Oslo, Moscow, Russia. kopnin@imb.ac.ru
authors.forename: P B
authors.initials: PB
authors.lastname: Kopnin
authors.forename: A V
authors.initials: AV
authors.lastname: Ivanov
authors.forename: G V
authors.initials: GV
authors.lastname: Il'inskaia
authors.forename: A A
authors.initials: AA
authors.lastname: Sablina
authors.forename: B P
authors.initials: BP
authors.lastname: Kopnin
authors.forename: P M
authors.initials: PM
authors.lastname: Chumakov
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology*; D005786:Gene Expression Regulation; D011905:Genes, ras; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D018631:ras Proteins