title: Absence of point mutations at codon 17 of the mdm2 gene (serine 17) in human primary tumors.
abstract: Mdm2 is a phosphoprotein that interacts with protein p53, inhibiting its activity. A serine located in position 17 of Mdm2, has been implicated in its phosphorylation process. We hypothesize that point mutations at serine 17 could block its phosphorylation and thereby increase the p53-Mdm2 interaction. This mechanism could increase the p53 degradation and cause a loss of the protective effect of p53 against tumorigenesis. This hypothesis was based on recent studies in vitro, demonstrating that when serine 17 is mutated, the DNA-dependent protein kinase, activated by genomic damage, is unable to phosphorylate it. Thus, we investigated whether structural point mutations at exon 3 of the Mdm2 gene, affecting codon 17, were present in 162 human primary tumors, 70 breast carcinomas, 14 bladder tumors, 18 colon adenocarcinomas and 60 testicular tumors. Direct sequencing of a fragment (204 bp) of exon 3 of the Mdm2 gene that contains the codon 17 showed no mutations at this position, independently of the presence or absence of p53 gene mutations in the same tumors. These results do not support the hypothesis that mutations in the Mdm2 gene at this level are involved in the tumorigenic process of human cancers.
authors.affiliation: Department of Medical Oncology, Clinica Puerta de Hierro, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Silva
authors.forename: J M
authors.initials: JM
authors.lastname: Silva
authors.forename: G
authors.initials: G
authors.lastname: Dominguez
authors.forename: J M
authors.initials: JM
authors.lastname: Garcia
authors.forename: O
authors.initials: O
authors.lastname: Rodriguez
authors.forename: C
authors.initials: C
authors.lastname: Garcia-Andrade
authors.forename: J
authors.initials: J
authors.lastname: Cuevas
authors.forename: M
authors.initials: M
authors.lastname: Provencio
authors.forename: P
authors.initials: P
authors.lastname: España
authors.forename: F
authors.initials: F
authors.lastname: Bonilla
mesh_terms: D003062:Codon; D016158:Genes, p53; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D009687:Nuclear Proteins; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2
chemical_list: D003062:Codon; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2