A novel dysfunctional p53 mutation in the human neuroblastoma cell line TGW.
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.
Sugiyama
Hisahiko
H
Department of Molecular Biology, Toho University Faculty of Medicine, Tokyo 143-8540, Japan.
Arita
Michitsune
M
Min
Zhenghua
Z
Zhong
Xioling
X
Iwasaki
Iwao
I
Hirano
Keihachiro
K
Shimatake
Hiroyuki
H
Hemmi
Hiromichi
H
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
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)