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 obs...

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Veröffentlicht in:Cell death and differentiation 1999-04, Vol.6 (4), p.326-333
Hauptverfasser: Rakkar, A N, Katayose, Y, Kim, M, Craig, C, Ohri, E, Li, Z, Cowan, K H, Seth, P
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container_end_page 333
container_issue 4
container_start_page 326
container_title Cell death and differentiation
container_volume 6
creator Rakkar, A N
Katayose, Y
Kim, M
Craig, C
Ohri, E
Li, Z
Cowan, K H
Seth, P
description 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.
doi_str_mv 10.1038/sj.cdd.4400498
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subjects Adenoviridae
Adenoviridae Infections
APO-1 protein
Apoptosis - genetics
Breast Neoplasms
CD95 antigen
Cytotoxins - genetics
DNA Primers
DNA, Neoplasm - analysis
Fas antigen
fas Receptor - genetics
Female
Gene Expression
Genetic Therapy - methods
Genetic Vectors
human adenovirus
Humans
Lung Neoplasms
Tumor Cells, Cultured - chemistry
Tumor Cells, Cultured - cytology
Tumor Cells, Cultured - virology
Tumor Suppressor Protein p53 - physiology
title A novel adenoviral vector expressing human Fas/CD95/APO-1 enhances p53-mediated apoptosis
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