An AR-Skp2 pathway for proliferation of androgen-dependent prostate-cancer cells

Hongbo Wang, Daqian Sun, Peng Ji, James Mohler, Liang Zhu

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Androgen-androgen-receptor (androgen-AR) signaling in normal prostate epithelium promotes terminal luminal epithelial cell differentiation. In androgen-dependent prostate-cancer cells, androgen-AR signaling gains the ability to promote both differentiation and proliferation. How this signaling promotes proliferation of androgen-dependent prostate-cancer cells and its relationship with the differentiation-promoting functions of the AR are important issues regarding the biology of androgen-dependent prostate-cancer cells. Herein, we report the identification of an AR-Skp2 pathway in prostate-cancer cells that depend on the AR for proliferation; in this pathway, AR is a robust upstream regulator of Skp2 through blocking the D-box-dependent degradation of this protein, and Skp2, in turn, serves as an essential downstream effector of AR in promoting proliferation independently of the differentiation-promoting function of AR. These results provide new knowledge on how AR functions in androgen-dependent prostate-cancer cells and identify strategies to specifically target the proliferation-promoting function of AR without compromising cancer-cell differentiation.

Original languageEnglish (US)
Pages (from-to)2578-2587
Number of pages10
JournalJournal of cell science
Volume121
Issue number15
DOIs
StatePublished - Aug 1 2008

Keywords

  • Androgen receptor
  • Androgen-dependent proliferation
  • D-box-dependent degradation
  • Prostate-cancer cells
  • Skp2

ASJC Scopus subject areas

  • Cell Biology

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