Altered prostatic epithelial proliferation and apoptosis, prostatic development, and serum testosterone in mice lacking cyclin-dependent kinase inhibitors

Motoko Mukai, Qiang Dong, Matthew P. Hardy, Hiroaki Kiyokawa, Richard E. Peterson, Paul S. Cooke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Normal prostatic development and some prostatic diseases involve altered expression of the cell-cycle regulators p27 and p21 (also known as CDKN1B and CDKN1A, respectively). To determine the role of these proteins in the prostate, we examined prostatic phenotype and development in mice lacking p27 and/or p21. In p27-knockout (p27KO) mice, epithelial proliferation was increased 2- and 3.8-fold in the ventral and dorsolateral prostate, respectively, versus wild-type (WT) mice, although prostatic weights were not different. Epithelial apoptosis was increased in p27KO mice and may account for the lack of a concurrent increase in weight. Testosterone deficiency observed in this group was not the cause of this increase, because vehicle- and testosterone-treated p27KO mice had similar percentages of apoptotic cells. Also observed was a trend toward a decreased functional epithelial cytodifferentiation, indicating a potential role of p27 in this process. Conversely, dorsolateral prostate and seminal vesicle (SV) of p21-knockout (p21KO) mice, and all prostatic lobes and SV of p21/p27 double-knockout mice, weighed significantly less compared to the WT mice, and their epithelial proliferation was normal. Decreased testosterone concentrations may contribute to the decreased prostatic weights. However, other factors may be involved, because testosterone replacement only partially restored prostatic weights. We conclude that loss of p27 increases prostatic epithelial proliferation and alters differentiation but does not result in prostatic hyperplasia because of increased epithelial cell loss. The p21 KO mice showed phenotypes distinctly different from those of p27KO mice, suggesting nonredundant roles of p21 and p27 in prostatic development. Loss of p27 or of both p21 and p27 results in serum testosterone deficiency, complicating analysis of the prostatic effects of these cell-cycle regulators.

Original languageEnglish (US)
Pages (from-to)951-958
Number of pages8
JournalBiology of reproduction
Volume73
Issue number5
DOIs
StatePublished - Nov 2005

Keywords

  • Apoptosis
  • Male reproductive tract
  • Prostate
  • Testosterone

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

Fingerprint Dive into the research topics of 'Altered prostatic epithelial proliferation and apoptosis, prostatic development, and serum testosterone in mice lacking cyclin-dependent kinase inhibitors'. Together they form a unique fingerprint.

Cite this