Cell proliferation, DNA repair, and p53 function are not required for programmed death of prostatic glandular cells induced by androgen ablation

R. R. Berges, Y. Furuya, L. Remington, H. F. English, T. Jacks, J. T. Isaacs

Research output: Contribution to journalArticlepeer-review

Abstract

Androgen ablation induces programmed death of androgen-dependent prostatic glandular cells, resulting in fragmentation of their genomic DNA and the cells themselves into apoptotic bodies. Twenty percent of prostatic glandular cells undergo programmed death per day between day 2 and 5 after castration. During this same period, <1% of prostatic glandular cells enter the S phase of the cell cycle, documenting that >95% of these die in G0. During the programmed death of these G0 glandular cells, a futile DNA repair process is induced secondary to the DNA fragmentation. This futile DNA repair is not required, however, since inhibition of this process by >90% with an appropriately timed hydroxyurea dosing regimen had no effect upon the extent of the programmed death of these cells after castration. Likewise, p53 gene expression is not required since the same degree of cell death occurred in prostates and seminal vesicles after castration of wild-type and p53- deficient mice.

Original languageEnglish (US)
Pages (from-to)8910-8914
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number19
DOIs
StatePublished - 1993

Keywords

  • DNA damage
  • S-phase progression
  • apoptosis

ASJC Scopus subject areas

  • General

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