Studies on the molecular mechanism of growth inhibition with p53 adenoviral construct in human ovarian cancer

K. Mujoo, J. J. Catino, D. C. Maneval, J. U. Gutterman

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Advanced stage human ovarian cancer exhibits 50-60% mutation of the p53 tumor suppressor gene. We introduced the wild-type p53 gene into the cells using a replication deficient recombinant adenovirus for p53 gene therapy. p53-adenovirus (rAd-p53) inhibited the growth of a number of ovarian cancer cells, which correlated well with the transduction of adenovirus containing β-galactosidase reporter gene in the tested cell lines. Results presented herein demonstrate that p53 induced the expression of CDK inhibitor WAF1/CIP1/p21 in human ovarian cancer cells with null or mutant p53. p53 incorporation also induced the expression of mdm-2 and bax proteins in human ovarian cancer cells. In contrast, we were unable to detect the expression of bcl-2 protein in the tested cells, and the expression bcl-x(L) in the tested human ovarian cells was not altered post-infection of cells with rAd-p53. Cell cycle analysis revealed pronounced G1 arrest 24 h post-infection with rAd-p53 in human ovarian cancer cells with only a small percentage of cells (-2%) undergoing apoptosis. rAd-p53 (p53-adenovirus) inhibited the growth of established subcutaneous xenograft tumors (OVCAR-3) of human ovarian carcinoma and completely regressed the tumors in 5/8 mice, indicating a potential for p53 tumor suppressor gene therapy in human ovarian cancer.

Original languageEnglish (US)
Pages (from-to)233-241
Number of pages9
JournalInternational Journal of Gynecological Cancer
Volume8
Issue number3
DOIs
StatePublished - 1998

Keywords

  • Bcl-2 family
  • Cell cycle
  • P21/WAF1
  • P53
  • Xenograft models

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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