A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia

Paloma Alonso-Magdalena, Clemens Brössner, Angelika Reiner, Guojun Cheng, Nobuhiro Sugiyama, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Benign prostatic hyperplasia (BPH) is usually described as a pathological proliferation of prostatic fibroblasts/myofibroblasts and epithelial cells. In the present study of BPH samples, we have made a morphological and immunohistochemical study of BPH prostatic sections using markers of proliferation, apoptosis, hormone receptors, and TGFβ signaling. We found no evidence of proliferation in the stroma but in the epithelium of some ducts; 0.7% of the basal and 0.4% of luminal cells were positive for Ki67 and PCNA Androgen receptor and estrogen receptor beta (ERβ)1 and ERβcx were abundant in both stromal and epithelial compartments but cells expressing ERα were very rare. What was very common in all BPH samples was the following: (i) regions of the ductal epithelium where the epithelial cells did not express E-cadherin, had lost their polarization, and become spindle shaped (the nuclei of these cells were strongly positive for pSmad 3 and Snail); and (ii) regions where the walls of the blood vessels were extremely thick and there was loss of endothelial layer. Loss of E-cadherin, increased pSmad 3, and high expression of Snail are all characteristic of epithelial-mesenchymal transition (EMT). We conclude that BPH is not a disease of prostatic stromal proliferation but rather of accumulation of mesenchymal-like cells derived from the prostatic epithelium and the endothelium. TGFβ is thought to play a key role in EMT. Our data suggests that TGF-β/Smad should be considered as targets for treatment of BPH.

Original languageEnglish (US)
Pages (from-to)2859-2863
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number8
DOIs
StatePublished - Feb 24 2009

Keywords

  • Proliferation
  • TGF beta signaling

ASJC Scopus subject areas

  • General

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