Tumor-selective transgene expression in vivo mediated by an E2F-responsive adenoviral vector

Nat Med. 1997 Oct;3(10):1145-9. doi: 10.1038/nm1097-1145.


Recent data suggest that many tumors, such as malignant gliomas, have disrupted pRB function, either because of RB-1 gene mutations or as a result of mutations affecting upstream regulators of pRB such as cyclin D1 or p16/INK4a/MTS1 (ref. 1-5). Tumor suppression by pRB has been linked to its ability to repress E2F-responsive promoters such as the E2F-1 promoter. Thus, a prediction, which has not yet been demonstrated experimentally in vivo, is that E2F-responsive promoters should be more active in tumor cells relative to normal cells because of an excess of "free" E2F and loss of pRB/E2F repressor complexes. We demonstrate that adenoviral vectors that contain transgenes driven by the E2F-1 promoter can mediate tumor-selective gene expression in vivo, allowing for eradication of established gliomas with significantly less normal tissue toxicity than seen with standard adenoviral vectors. Our data indicate that de-repression of the E2F-1 promoter occurs in cancer cells in vivo, a finding that can be exploited to design viral vectors that mediate tumor-selective gene expression.

MeSH terms

  • Adenoviruses, Human*
  • Animals
  • Astrocytoma / pathology*
  • Brain / pathology
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy
  • Carrier Proteins*
  • Cell Cycle
  • Cell Cycle Proteins / biosynthesis
  • DNA-Binding Proteins / biosynthesis
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Genetic Therapy
  • Genetic Vectors*
  • Glioma / pathology*
  • Glioma / therapy
  • Promoter Regions, Genetic
  • Rats
  • Rats, Sprague-Dawley
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcription, Genetic
  • Transfection / methods*
  • Tumor Cells, Cultured
  • beta-Galactosidase / biosynthesis


  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2f1 protein, rat
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • beta-Galactosidase