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 language | English (US) |
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Pages (from-to) | 2578-2587 |
Number of pages | 10 |
Journal | Journal of cell science |
Volume | 121 |
Issue number | 15 |
DOIs | |
State | Published - Aug 1 2008 |
Keywords
- Androgen receptor
- Androgen-dependent proliferation
- D-box-dependent degradation
- Prostate-cancer cells
- Skp2
ASJC Scopus subject areas
- Cell Biology