A novel adenoviral vector expressing human Fas/CD95/APO-1 enhances p53-mediated apoptosis

Cell Death Differ. 1999 Apr;6(4):326-33. doi: 10.1038/sj.cdd.4400498.


Recent evidence suggests an intriguing link between p53 and the Fas pathway. To evaluate this association further, we utilized a recombinant adenoviral vector (AdWTp53) to overexpress wild-type p53 in lung cancer (A549, H23, EKVX and HOP92) and breast cancer (MDA-MB-231 and MCF-7) cell lines and observed an increase in the Fas/CD95/APO-1 protein levels. Furthermore, this increase correlated with the sensitivity of the cell lines to p53-mediated cytotoxicity. To examine the effects of Fas over-expression in cells resistant to p53 over-expression, we constructed AdFas, an adenoviral vector capable of transferring functional human Fas to cancer cells. Interestingly, infection of p53-resistant MCF-7 cells with AdFas sensitized them to p53-mediated apoptosis. These studies indicate that combined over-expression of Fas and wild-type p53 may be an effective cancer gene therapy approach, especially in cells relatively resistant to p53 over-expression.

MeSH terms

  • Adenoviridae Infections
  • Adenoviridae*
  • Apoptosis / genetics*
  • Breast Neoplasms
  • Cytotoxins / genetics
  • DNA Primers
  • DNA, Neoplasm / analysis
  • Female
  • Gene Expression
  • Genetic Therapy / methods
  • Genetic Vectors*
  • Humans
  • Lung Neoplasms
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / virology
  • Tumor Suppressor Protein p53 / physiology*
  • fas Receptor / genetics*


  • Cytotoxins
  • DNA Primers
  • DNA, Neoplasm
  • Tumor Suppressor Protein p53
  • fas Receptor