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

15 Citations (Scopus)

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

Fingerprint

Androgens
Prostatic Neoplasms
Androgen Receptors
Cell Differentiation
S-Phase Kinase-Associated Proteins
Proteolysis
Prostate
Epithelium
Epithelial Cells
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

An AR-Skp2 pathway for proliferation of androgen-dependent prostate-cancer cells. / Wang, Hongbo; Sun, Daqian; Ji, Peng; Mohler, James; Zhu, Liang.

In: Journal of Cell Science, Vol. 121, No. 15, 01.08.2008, p. 2578-2587.

Research output: Contribution to journalArticle

Wang, Hongbo ; Sun, Daqian ; Ji, Peng ; Mohler, James ; Zhu, Liang. / An AR-Skp2 pathway for proliferation of androgen-dependent prostate-cancer cells. In: Journal of Cell Science. 2008 ; Vol. 121, No. 15. pp. 2578-2587.
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