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 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.
Rakkar
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AN
Medical Breast Cancer Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institues of Health, Bethesda, Maryland 20892, USA.
Katayose
Y
Y
Kim
M
M
Craig
C
C
Ohri
E
E
Li
Z
Z
Cowan
K H
KH
Seth
P
P
D000256:Adenoviridae; D000257:Adenoviridae Infections; D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms; D003603:Cytotoxins / Q000235:genetics; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D019014:fas Receptor / Q000235:genetics*
D003603:Cytotoxins; D017931:DNA Primers; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor