Epithelial-to-mesenchymal transition and estrogen receptor α mediated epithelial dedifferentiation mark the development of benign prostatic hyperplasia

Rui Shao, Jiandang Shi*, Haitao Liu, Xiaoyu Shi, Xiaoling Du, Helmut Klocker, Chung Lee, Yan Zhu, Ju Zhang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

BACKGROUND Epithelial-to-mesenchymal transition (EMT) has been reported involved in the pathogenesis of fibrotic disorders and associated with stemness characteristics. Recent studies demonstrated that human benign prostatic hyperplasia (BPH) development involves accumulation of mesenchymal-like cells derived from the prostatic epithelium. However, the inductive factors of EMT in the adult prostate and the cause-and-effect relationship between EMT and stemness characteristics are not yet resolved. METHODS EMT expression patterns were immunohistochemically identified in the human epithelia of normal/BPH prostate tissue and in a rat BPH model induced by estrogen/androgen (E2/T, ratio 1:100) alone or in the presence of the ER antagonist raloxifene. Gene expression profiles were analyzed in micro-dissected prostatic epithelia of rat stimulated by E2/T for 3 days. RESULTS Two main morphological features both accompanied with EMT were observed in the epithelia of human BPH. Luminal cells undergoing EMT dedifferentiated from a cytokeratin (CK) CK18+/ CK8+/CK19+ to a CK18-/CK8+/CK19 - phenotype and CK14 expression increased in basal epithelial cells. ERα expression was closely related to these dedifferentiated cells and the expression of EMT markers. A similar pattern of EMT events was observed in the E2/T induced rat model of BPH in comparison to the prostates of untreated rats, which could be prevented by raloxifene. CONCLUSIONS Epithelial and mesenchymal phenotype switching is an important mechanism in the etiology of BPH. ERα mediated enhanced estrogenic effect is a crucial inductive factor of epithelial dedifferentiation giving rise to activation of an EMT program in prostate epithelium. Prostate 74:970-982, 2014.

Original languageEnglish (US)
Pages (from-to)970-982
Number of pages13
JournalProstate
Volume74
Issue number9
DOIs
StatePublished - Jun 2014

Keywords

  • benign prostatic hyperplasia
  • embryonic myosin
  • epithelial-mesenchymal transition
  • estrogen receptor α

ASJC Scopus subject areas

  • Oncology
  • Urology

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