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

Amol N.S. Rakkar, Yu Katayose, Min Kim, Caroline Craig, Ekta Ohri, Zhuangwu Li, Kenneth H. Cowan, Prem Seth

Research output: Contribution to journalArticle

21 Scopus citations

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 overexpression.

Original languageEnglish (US)
Pages (from-to)326-333
Number of pages8
JournalCell Death and Differentiation
Volume6
Issue number4
DOIs
StatePublished - Apr 1999

Keywords

  • Adenovirus
  • Apoptosis
  • Fas/CD95/APO-1
  • Gene therapy
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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