E-cadherin-mediated survival of androgen-receptor-expressing secretory prostate epithelial cells derived from a stratified in vitro differentiation model

Laura E. Lamb, Beatrice S. Knudsen, Cindy K. Miranti

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

The androgen receptor (AR) is expressed in differentiated secretory prostate epithelial cells in vivo. However, in the human prostate, it is unclear whether androgens directly promote the survival of secretory cells, or whether secretory cells survive through androgen-dependent signals from the prostate stroma. Biochemical and mechanistic studies have been hampered by inadequate cell-culture models. In particular, large-scale differentiation of prostate epithelial cells in culture has been difficult to achieve. Here, we describe the development of a differentiation system that is amenable to functional and biochemical analysis and its application to deciphering the survival pathways in differentiated AR-expressing epithelial cells. Confluent prostate epithelial cell cultures were treated with keratinocyte growth factor (KGF) and dihydrotestosterone. After 2 weeks, a suprabasal cell layer was formed in which cells no longer expressed α2, α3, α6, αv, α1 or α4 integrins or p63, K5, K14, EGFR, FGFR2IIIb or Bcl-2, but instead expressed AR and androgen-induced differentiation markers, including K18, K19, TMPRSS2, Nkx3.1, PMSA, KLK2 and secreted prostate-specific antigen (PSA). Differentiated prostate cell survival depended on E-cadherin and PI3K, but not KGF, androgen, AR or MAPK. Thus survival of differentiated prostate epithelial cells is mediated by cell-cell adhesion, and not through androgen activity or prostate stroma-derived KGF.

Original languageEnglish (US)
Pages (from-to)266-276
Number of pages11
JournalJournal of Cell Science
Volume123
Issue number2
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Androgen receptor
  • Differentiation
  • Epithelial
  • Prostate
  • Secretory cells
  • Survival

ASJC Scopus subject areas

  • Cell Biology

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