Overexpression of the E2F-1 transcription factor gene mediates cell transformation.
The E2F transcription factor can regulate expression of numerous cellular genes controlling proliferation, including proto-oncogenes and genes regulating cell cycle progression. Therefore, genes comprising the E2F gene family could potentially contribute to carcinogenesis. To test the potential of E2F to act as a transforming gene, a cDNA encoding E2F-1 was constitutively overexpressed in established rodent cells using a retroviral vector. Overexpressed E2F-1 was functional, as shown by stimulation of a transfected adenovirus E2 promoter driving a chloramphenicol acetyltransferase reporter gene in E2F-1 overexpressing cells. This stimulation was dependent on functional E2F binding sites in the promoter. Examination of phenotype showed that E2F-1 overexpression mediated cell transformation as measured by the ability of cells to form colonies in soft agar medium. In addition, overexpressed E2F-1 shortened the duration of the G1 cell cycle phase in proliferating cells, a property characteristic of other transforming genes. These data provide direct evidence that E2F-1 can act as a transforming gene and a critical regulator of cell cycle progression and suggest the possibility of E2F involvement in carcinogenesis.
Yang
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XH
Department of Microbiology and Immunology, Finch University of Health Sciences, Chicago Medical School, IL 60064-3095, USA.
Sladek
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D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016193:G1 Phase / Q000502:physiology; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000502:physiology; D056465:Retinoblastoma-Binding Protein 1; D012190:Retroviridae / Q000235:genetics; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection; D014410:Tumor Stem Cell Assay
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase