The androgen receptor can promote beta-catenin nuclear translocation independently of adenomatous polyposis coli.
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.
Mulholland
David J
DJ
Prostate Research Centre, 2660 Oak St., Jack Bell Research, Vancouver General Hospital, Vancouver, British Columbia V6H 3Z6, Canada. djm@interchange.ubc.ca
Cheng
Helen
H
Reid
Kim
K
Rennie
Paul S
PS
Nelson
Colleen C
CC
D021581:Active Transport, Cell Nucleus; D011125:Adenomatous Polyposis Coli / Q000378:metabolism*; D000727:Androgen-Binding Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D008297:Male; D015741:Metribolone / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D015534:Trans-Activators; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D000727:Androgen-Binding Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011944:Receptors, Androgen; D015534:Trans-Activators; D051176:beta Catenin; C027519:probasin; D015741:Metribolone; D004247:DNA; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3