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J. Biol. Chem. 277 (20): 17933-17943

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

The Androgen Receptor Can Promote beta -Catenin Nuclear Translocation Independently of Adenomatous Polyposis Coli*

David J. MulhollandDagger , Helen Cheng, Kim Reid, Paul S. Rennie, and Colleen C. Nelson

From the Prostate Research Centre, 2660 Oak St., Jack Bell Research, Vancouver General Hospital, Vancouver, British Columbia V6H 3Z6, Canada

We provide evidence that the androgen receptor (AR) can promote nuclear translocation of beta -catenin in LNCaP and PC3 prostate cancer cells. Using AR-expressing cells (LNCaP) and non-AR-expressing cells (PC3) we showed by time course cell fractionation that the AR can shuttle beta -catenin into the nucleus when exposed to exogenous androgen. Cells exposed to the synthetic androgen, R1881, show distinct, punctate, nuclear co-localization of the AR and beta -catenin. We further showed that the AR does not interact with adenomatous polyposis coli or glycogen synthase kinase-3beta and, therefore, conclude that androgen-mediated transport of beta -catenin occurs through a distinct pathway. The minimal necessary components of the AR and beta -catenin required for binding nuclear accumulation of beta -catenin nuclear import appears to be the DNA/ligand binding regions and the Armadillo repeats of beta -catenin. We also employed a novel DNA binding assay to illustrate that beta -catenin has the capacity to bind to the probasin promoter in an AR-dependent manner. The physiological relevance of AR-mediated transport of beta -catenin and binding to an AR promoter appeared to be a substantial increase in AR transcriptional reporter activity. AR-mediated import represents a novel mode of nuclear accumulation of beta -catenin.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Tel.: 604-875-5555 (ext. 61473); Fax: 604-875-5654; E-mail: djm@interchange.ubc.ca.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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