Stem cell features of benign and malignant prostate epithelial cells

Research output: Contribution to journalArticle

Abstract

Purpose: We present a new hypothesis suggesting that the different malignant potential of benign prostatic hyperplasia (BPH) and high grade prostatic intraepithelial neoplasia may be explained by distinct alterations in stem cell-like properties. Materials and Methods: We used our results and the recent literature to develop this hypothesis in the context of an updated prostate stem cell model. Results: While high grade prostatic intraepithelial neoplasia is a likely precursor lesion to many prostatic adenocarcinomas, BPH rarely if ever progresses directly to carcinoma. Prostate epithelium contains basal and secretory compartments. Secretory cells appear to differentiate from basal cells. Thus, prostatic stem cells most likely reside in the basal compartment. In BPH there is a slight increase in epithelial proliferation, yet most replicating epithelial cells within BPH maintain their normal restriction to the basal compartment. In high grade prostatic intraepithelial neoplasia there is a marked increase in cell proliferation. In contrast to BPH, the majority of proliferating cells in high grade prostatic intraepithelial neoplasia reside in the secretory compartment. The biological significance of this topographic infidelity of proliferation in high grade prostatic intraepithelial neoplasia remains unclear but may relate mechanistically to down regulation of the cyclin dependent kinase inhibitor, p27(kip1). Normal basal cells express GSTP1, an enzyme that inactivates reactive electrophiles and organic hydroperoxides, and that may protect cells from deoxyribonucleic acid damaging agents. In contrast, normal secretory cells and high grade prostatic intraepithelial neoplasia cells do not express this enzyme. Conclusions: We propose that topographic infidelity of proliferation produces a population of secretory cells replicating in the absence of key genome protective mechanisms, thus setting the stage for an accumulation of genomic alterations and instability in high grade prostatic intraepithelial neoplasia. This action occurs along with activation of telomerase, resulting in an immortal clone capable of developing into invasive carcinoma. The model predicts that genome protection remains intact in BPH, minimizing its malignant potential.

Original languageEnglish (US)
Pages (from-to)2381-2392
Number of pages12
JournalJournal of Urology
Volume160
Issue number6 II
DOIs
StatePublished - Dec 1998

Fingerprint

Prostatic Intraepithelial Neoplasia
Prostate
Prostatic Hyperplasia
Stem Cells
Epithelial Cells
Genome
Cyclin-Dependent Kinase Inhibitor p27
Carcinoma
Genomic Instability
Telomerase
Enzymes
Hydrogen Peroxide
Adenocarcinoma
Down-Regulation
Epithelium
Clone Cells
Cell Proliferation
DNA

Keywords

  • Cyclins
  • Prostatic hypertrophy
  • Prostatic neoplasms
  • Stem cells
  • Transferases

ASJC Scopus subject areas

  • Urology

Cite this

Stem cell features of benign and malignant prostate epithelial cells. / Demarzo, Angelo Michael; Nelson, William G; Meeker, Alan Keith; Coffey, Donald S.

In: Journal of Urology, Vol. 160, No. 6 II, 12.1998, p. 2381-2392.

Research output: Contribution to journalArticle

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