title: A novel dysfunctional p53 mutation in the human neuroblastoma cell line TGW.
abstract: Mutations of p53 are rare in primary and advanced neuroblastomas. The p53 gene was studied in a TGW cell line established from a TNB1 xenograft, derived from metastasized neuroblastoma. The p53 protein level in TGW was elevated at baseline. Treatment with doxorubicin to induce genotoxic stress neither altered the p53 protein level nor induced p21 protein within 24 hours. DNA sequencing analysis revealed a novel triplet deletion mutation at codon 282 (R282del) of the p53 gene, a mutation also found in TNB1, indicating that the mutation occurred in the relapsed tumor. The mutant was incapable of transactivation and had no effect on the transactivational activity of the wild-type p53 gene product in reporter assays using a plasmid possessing a p53 responsive element of p21, bax or mdm2. These results suggest that the mutant p53R282del found in TGW is a non-functional mutant and has no dominant negative nature.
authors.affiliation: Department of Molecular Biology, Toho University Faculty of Medicine, Tokyo 143-8540, Japan.
authors.forename: Hisahiko
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Michitsune
authors.initials: M
authors.lastname: Arita
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Min
authors.forename: Xioling
authors.initials: X
authors.lastname: Zhong
authors.forename: Iwao
authors.initials: I
authors.lastname: Iwasaki
authors.forename: Keihachiro
authors.initials: K
authors.lastname: Hirano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimatake
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Hemmi
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D003062:Codon; D004252:DNA Mutational Analysis; D018450:Disease Progression; D017930:Genes, Reporter; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D012008:Recurrence; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D003062:Codon; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D015689:Oncogene Protein p21(ras)