Cytotoxic Effects of Adenovirus-mediated Wild-Type p53 Protein Expression in Normal and Tumor Mammary Epithelial Cells

Dai Katayose, Jean Gudas, Hoang Nguyen, Kenneth H. Cowan, Prem Seth

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

To evaluate the effects of the wild-type p53 expression in normal and tumor cells, we have constructed a recombinant adenovirus vector (El minus) expressing human wild-type p53 cDNA (AdWTp53). Infection of normal and tumor cells of lung and mammary epithelial origin with AdWTp53 resulted in high levels of wild-type p53 expression. Production of p53 protein following infection was dependent on the dose of AdWTp53 with maximum amounts of p53 produced following infection with 50 plaque-forming units/cell. Ad-WTp53 infection inhibited the growth of all human cell lines studied. However, tumor cells that were null for p53 prior to infection (H-358 and MDA-MB-157) and tumor cells that expressed mutant endogenous p53 protein (MDA-MB-231 and MDA-MB-453) were more sensitive to AdWTp53 cytotoxicity than cells that contained the wild-type p53 (MCF-7, MCF-10, 184B5, and normal mammary epithelial cells). All cells exhibited WAFl/Cip1 mRNA and protein induction following AdWTp53 infection. AdWTp53-induced cytotoxicity of human tumor cell lines expressing mutant p53 was mediated by apoptosis as revealed by nucleosomal DNA fragmentation analysis. No detectable nucleosomal DNA fragmentation was observed following AdWTp53 infection of human cells expressing wild-type p53. These data suggest that endogenous p53 status is a determinant of AdWTp53- mediated cell killing of human tumor cells.

Original languageEnglish (US)
Pages (from-to)889-897
Number of pages9
JournalClinical Cancer Research
Volume1
Issue number8
Publication statusPublished - Aug 1 1995

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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