Insulin-like growth factor-I produced by seminal vesicles: relationship to intraepithelial basal cell hyperplasia in the prostate

Clin Cancer Res. 2007 Jun 1;13(11):3140-6. doi: 10.1158/1078-0432.CCR-06-2607.

Abstract

Purpose: This study examined the seminal vesicle fluid (SVF) as a potential local source of insulin-like growth factor-I (IGF-I) in the peripheral zone of the prostate.

Experimental design: IGF-I levels in seminal fluid were measured. The levels of the IGF-I receptor (IGF-IR) in its active, phosphorylated form as well as direct downstream targets were examined in the peripheral zone of the prostate.

Results: In situ, we find that the IGF-IR is activated in the peripheral zone in areas of atrophy, prostatic intraepithelial hyperplasia, and cancer. In addition, immunostaining reveals preferential activation of the IGF-IR in p63-positive cells in areas of intermediate basal cell hyperplasia in the peripheral zone, indicating that prostate progenitor cells are highly sensitive to increases in local IGF-I levels. These areas of basal cell hyperplasia occur at high incidence in the peripheral zone of the prostate. Relatively high levels of IGF-I were identified in SVF. In addition, we find that SVF can stimulate the proliferation of both normal and cancer-derived prostate cells.

Conclusions: These results suggest that SVF is a local source of IGF-I that provides chronic stimulation of prostate cells. This chronic stimulation could contribute to the development of prostate cancer in older men.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / physiology*
  • Male
  • Membrane Proteins / metabolism
  • Phosphorylation
  • Prostate / metabolism
  • Prostatic Hyperplasia / metabolism*
  • Prostatic Neoplasms / metabolism
  • Receptor, IGF Type 1 / metabolism*
  • Seminal Vesicles / metabolism*
  • Signal Transduction

Substances

  • CKAP4 protein, human
  • Membrane Proteins
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1