Established cell lines transformed by E2F-1 overexpression contain wild-type p53.
Overexpression of genes encoding E2F transcription factors can transform some cultured cell lines and cause apoptosis of others. Apoptosis due to E2F overexpression requires the presence of wild-type p53. Cell lines in which stable E2F overexpression is possible might be expected, therefore, to contain mutant p53. In this report, it was asked whether endogenous p53 was mutant or wild-type in four established fibroblast cell lines that this laboratory previously showed stably overexpressed and were transformed by exogenous E2F-1. Unexpectedly, it was found that the p53 in these cells was wild-type by the criteria of immunoprecipitation with conformation-specific, p53 monoclonal antibodies and by transactivation of a p53-dependent reporter gene construct in transient transfection assays. These data indicate that stable overexpression of E2F-1 is possible in the presence of wild-type p53 and may result in cell transformation.
Sladek
T L
TL
Department of Microbiology and Immunology, Finch University of Health Sciences, Chicago Medical School, Illinois 60064-3095, USA. sladekt@mis.finchcms.edu
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D051379:Mice; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53