Adenovirus-mediated p53 growth inhibition of ovarian cancer cells is independent of endogenous p53 status

Judith K. Wolf, Gordon Mills, Lisa Bazzet, Robert C. Bast, Jack A. Roth, David M. Gershenson

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Objective. The aim of this study was to determine the effect of transfection of adenovirus-mediated wild-type p53 into ovarian cancer cells with both wild-type and mutant endogenous p53. Study design. Eight human ovarian cancer cell lines were used: three with p53 mutations, one that is p53 null, and four with wild-type p53. The recombinant p53 adenovirus (Adp53) contains the cytomegalovirus promoter, Wild-type p53 cDNA, and SV40 polyadenylation signal in a minigene cassette inserted into the E1-deleted region of modified Ad5. The transduction efficiency of cells was assessed using a β-gal-containing adenovirus. Cell-counting assays were used to evaluate the effect of transfection with Adp53 on the growth of cells. P53 expression was evaluated using Western blot. Cell cycle analysis and apoptosis studies were done using a tunnel-based assay and fluorescent activated cell sorting. Results. Transduction efficiencies varied between cell lines. More than 90% growth inhibition occurred in seven of eight cell lines after infection with adenovirus-mediated p53 if a viral dose leading to at least 50% of cells infected was used. Regardless of endogenous p53 status, apoptosis occurred in cells infected with p53. Conclusions. Ovarian cancer cells are growth inhibited by transfection with adenovirus-mediated p53 regardless of their endogenous p53 status. Growth inhibition is related to transduction efficiency.

Original languageEnglish (US)
Pages (from-to)261-266
Number of pages6
JournalGynecologic Oncology
Volume75
Issue number2
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

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Adenoviridae
Ovarian Neoplasms
Growth
Transfection
Cell Line
Apoptosis
Adenoviridae Infections
Polyadenylation
Cytomegalovirus
Cell Cycle
Complementary DNA
Western Blotting
Mutation

Keywords

  • Gene therapy
  • Ovarian cancer
  • Wild-type p53

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Adenovirus-mediated p53 growth inhibition of ovarian cancer cells is independent of endogenous p53 status. / Wolf, Judith K.; Mills, Gordon; Bazzet, Lisa; Bast, Robert C.; Roth, Jack A.; Gershenson, David M.

In: Gynecologic Oncology, Vol. 75, No. 2, 01.01.1999, p. 261-266.

Research output: Contribution to journalArticle

Wolf, Judith K. ; Mills, Gordon ; Bazzet, Lisa ; Bast, Robert C. ; Roth, Jack A. ; Gershenson, David M. / Adenovirus-mediated p53 growth inhibition of ovarian cancer cells is independent of endogenous p53 status. In: Gynecologic Oncology. 1999 ; Vol. 75, No. 2. pp. 261-266.
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abstract = "Objective. The aim of this study was to determine the effect of transfection of adenovirus-mediated wild-type p53 into ovarian cancer cells with both wild-type and mutant endogenous p53. Study design. Eight human ovarian cancer cell lines were used: three with p53 mutations, one that is p53 null, and four with wild-type p53. The recombinant p53 adenovirus (Adp53) contains the cytomegalovirus promoter, Wild-type p53 cDNA, and SV40 polyadenylation signal in a minigene cassette inserted into the E1-deleted region of modified Ad5. The transduction efficiency of cells was assessed using a β-gal-containing adenovirus. Cell-counting assays were used to evaluate the effect of transfection with Adp53 on the growth of cells. P53 expression was evaluated using Western blot. Cell cycle analysis and apoptosis studies were done using a tunnel-based assay and fluorescent activated cell sorting. Results. Transduction efficiencies varied between cell lines. More than 90{\%} growth inhibition occurred in seven of eight cell lines after infection with adenovirus-mediated p53 if a viral dose leading to at least 50{\%} of cells infected was used. Regardless of endogenous p53 status, apoptosis occurred in cells infected with p53. Conclusions. Ovarian cancer cells are growth inhibited by transfection with adenovirus-mediated p53 regardless of their endogenous p53 status. Growth inhibition is related to transduction efficiency.",
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