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

Recent evidence suggests an intriguing link between p53 and the Fas pathway . To evaluate this association further, we utilized a recombinant adenovira l 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 obse rved an increase in the Fas/CD95/APO-1 protein levels. Furthermore, this in crease correlated with the sensitivity of the cell lines to p53-mediated cy totoxicity, To examine the effects of Fas over-expression in cells resistan t to p53 over-expression, we constructed AdFas, an adenoviral vector capabl e of transferring functional human Fas to cancer cells. Interestingly, infe ction of p53 resistant MCF-7 cells with AdFas sensitized them to p53-mediat ed apoptosis, These studies indicate that combined over-expression of Fas a nd wild-type p53 may be an effective cancer gene therapy approach, especial ly in cells relatively resistant to p53 overexpression.