Transduction and apoptosis induction in the rat prostate, using adenovirus vectors

Wayne Kirkman, Ping Chen, Rosanna Schroeder, Mark R. Feneley, Ronald Rodriguez, Thomas J. Wickham, C. Richter King, Joseph T. Bruder

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Proapoptotic adenovirus vectors offer great promise for the treatment of cancer and nonmalignant conditions. Benign prostate hyperplasia (BPH) is a common nonmalignant enlargement of the prostate that involves epithelial, stromal, and smooth muscle components of the gland. We tested the hypothesis that an adenovirus vector expressing Fas ligand can be used to induce apoptosis in the prostate. We analyzed the efficiency of transduction and apoptosis induction in primary cultures of human prostate cells after adenovirus-mediated gene transfer. Efficient transduction was observed in primary prostate epithelial cells. Stromal and smooth muscle cells were more difficult to transduce, as no coxsackie-adenovirus receptor (CAR) expression was detectable on these cells. However, transduction was achieved in these cells when the multiplicity of infection was increased to 100 focal-forming units per cell, or when the vectors were delivered as calcium phosphate precipitates. Infection of all three primary prostate cell types with an adenovirus vector that expresses Fas ligand (AdFasL/G) resulted in rapid apoptosis. Direct injection of the rat prostate with an adenovirus vector carrying luciferase resulted in substantial luciferase expression. TUNEL analysis demonstrated that AdFasL/G administration induced low-level apoptosis in prostatic epithelial cells throughout the gland. As a first step toward enhancing the efficiency of prostate transductionin vivo, we tested an adenovirus vector that was engineered to have an expanded tropism. This vector, AdZ.F2K(pK7), was 10- to 500-fold more efficient than unmodified vectors in transducing prostate epithelial, smooth muscle, and stromal cells in culture. Moreover, AdZ.F2K(pK7) was more efficient than an unmodified vector at transducing the rat prostatein vivo, although the effect was dose dependent.

Original languageEnglish (US)
Pages (from-to)1499-1512
Number of pages14
JournalHuman Gene Therapy
Volume12
Issue number12
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Adenoviridae
Prostate
Apoptosis
Fas Ligand Protein
Luciferases
Prostatein
Smooth Muscle Myocytes
Coxsackie and Adenovirus Receptor-Like Membrane Protein
Epithelial Cells
Tropism
In Situ Nick-End Labeling
Stromal Cells
Infection
Hyperplasia
Smooth Muscle
Cell Culture Techniques
Injections
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Kirkman, W., Chen, P., Schroeder, R., Feneley, M. R., Rodriguez, R., Wickham, T. J., ... Bruder, J. T. (2001). Transduction and apoptosis induction in the rat prostate, using adenovirus vectors. Human Gene Therapy, 12(12), 1499-1512. https://doi.org/10.1089/10430340152480230

Transduction and apoptosis induction in the rat prostate, using adenovirus vectors. / Kirkman, Wayne; Chen, Ping; Schroeder, Rosanna; Feneley, Mark R.; Rodriguez, Ronald; Wickham, Thomas J.; King, C. Richter; Bruder, Joseph T.

In: Human Gene Therapy, Vol. 12, No. 12, 2001, p. 1499-1512.

Research output: Contribution to journalArticle

Kirkman, W, Chen, P, Schroeder, R, Feneley, MR, Rodriguez, R, Wickham, TJ, King, CR & Bruder, JT 2001, 'Transduction and apoptosis induction in the rat prostate, using adenovirus vectors', Human Gene Therapy, vol. 12, no. 12, pp. 1499-1512. https://doi.org/10.1089/10430340152480230
Kirkman, Wayne ; Chen, Ping ; Schroeder, Rosanna ; Feneley, Mark R. ; Rodriguez, Ronald ; Wickham, Thomas J. ; King, C. Richter ; Bruder, Joseph T. / Transduction and apoptosis induction in the rat prostate, using adenovirus vectors. In: Human Gene Therapy. 2001 ; Vol. 12, No. 12. pp. 1499-1512.
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