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First published online 15 July 2008
doi: 10.1242/jcs.030742

Journal of Cell Science 121, 2578-2587 (2008)
Published by The Company of Biologists 2008
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Research Article

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

Hongbo Wang1, Daqian Sun1, Peng Ji1, James Mohler2 and Liang Zhu1,*

1 Department of Developmental and Molecular Biology, The Albert Einstein Comprehensive Cancer Center and Liver Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2 Department of Urologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA

* Author for correspondence (e-mail: lizhu{at}aecom.yu.edu)

Accepted 20 May 2008

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.

Key words: Androgen receptor, Prostate-cancer cells, Skp2, D-box-dependent degradation, Androgen-dependent proliferation






© The Company of Biologists Ltd 2008