A novel adenoviral vector expressing human Fas/CD95/APO-1 enhances p53-mediated apoptosis. |
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Authors: | A N Rakkar Y Katayose M Kim C Craig E Ohri Z Li K H Cowan P Seth |
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Affiliation: | Medical Breast Cancer Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institues of Health, Bethesda, Maryland 20892, USA. |
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Abstract: | 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. |
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