In Vivo Gene Therapy with p53 or p21 Adenovirus for Prostate Cancer Academic Article uri icon

Overview

MeSH Major

  • Adenoviridae
  • Cyclins
  • Genes, p53
  • Genetic Therapy
  • Prostatic Neoplasms
  • Protein Kinase Inhibitors

abstract

  • We introduced the gene for wild-type human p53 or p21, a critical downstream mediator of p53-induced growth suppression, into a p53-deficient mouse prostate cancer cell line using a recombinant adenoviral vector (Ad5CMV-p53 or Ad5CMV-p21). Elevated levels of endogenous mouse p21 mRNA provided evidence for the functional activity of virally transduced p53. Functional activity of viral-transduced p21 was demonstrated through immunoprecipitation of cellular protein extracts, which showed that the viral-transduced p21 associates with cyclin-dependent kinase 2 and was sufficient to down-regulate the activity of the cyclin-dependent kinase by approximately 65%. In vitro growth assays revealed significantly higher growth suppression after Ad5CMV-p21 infection compared to Ad5CMV-p53. In vivo studies in syngeneic male mice with established s.c. prostate tumors demonstrated that the rate of growth and final tumor volume were reduced to a much greater extent in mice that received intratumor injection of Ad5CMV-p21 compared to Ad5CMV-p53. In addition, the survival of host animals bearing tumors that were infected with Ad5CMV-p21, but not Ad5CMV-p53, was significantly extended. These data suggest that Ad5CMV-p21 may be effective as a therapeutic agent for prostate cancer.

publication date

  • November 15, 1995

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 7585563

Additional Document Info

start page

  • 5151

end page

  • 5

volume

  • 55

number

  • 22