The androgen receptor can promote β-catenin nuclear translocation independently of adenomatous polyposis coli

被引:145
作者
Mulholland, DJ [1 ]
Cheng, H [1 ]
Reid, K [1 ]
Rennie, PS [1 ]
Nelson, CC [1 ]
机构
[1] Vancouver Gen Hosp, Prostate Res Ctr, Vancouver, BC V6H 3Z6, Canada
关键词
D O I
10.1074/jbc.M200135200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 B-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.
引用
收藏
页码:17933 / 17943
页数:11
相关论文
共 43 条
[1]  
Barker N, 2000, BIOESSAYS, V22, P961
[2]   Quantitation of androgen receptor gene expression in sporadic breast tumors by real-time RT-PCR:: evidence that MYC is an AR-regulated gene [J].
Bièche, I ;
Parfait, A ;
Tozlu, S ;
Lidereau, R ;
Vidaud, M .
CARCINOGENESIS, 2001, 22 (09) :1521-1526
[3]   Nucleocytoplasmic shuttling of the thyroid hormone receptor α [J].
Bunn, CF ;
Neidig, JA ;
Freidinger, KE ;
Stankiewicz, TA ;
Weaver, BS ;
McGrew, J ;
Allison, LA .
MOLECULAR ENDOCRINOLOGY, 2001, 15 (04) :512-533
[4]   IDENTIFICATION OF A CONSERVED REGION REQUIRED FOR HORMONE DEPENDENT TRANSCRIPTIONAL ACTIVATION BY STEROID-HORMONE RECEPTORS [J].
DANIELIAN, PS ;
WHITE, R ;
LEES, JA ;
PARKER, MG .
EMBO JOURNAL, 1992, 11 (03) :1025-1033
[5]   Cross-regulation of β-catenin-LEF/TCF and retinoid signaling pathways [J].
Easwaran, V ;
Pishvaian, M ;
Salimuddin ;
Byers, S .
CURRENT BIOLOGY, 1999, 9 (23) :1415-1418
[6]   Nuclear export of human β-catenin can occur independent of CRM1 and the adenomatous polyposis coli tumor suppressor [J].
Eleftheriou, A ;
Yoshida, M ;
Henderson, BR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (28) :25883-25888
[7]   THE STEROID AND THYROID-HORMONE RECEPTOR SUPERFAMILY [J].
EVANS, RM .
SCIENCE, 1988, 240 (4854) :889-895
[8]   The ABC of APC [J].
Fearnhead, NS ;
Britton, MP ;
Bodmer, WF .
HUMAN MOLECULAR GENETICS, 2001, 10 (07) :721-733
[9]   Subcellular localization of mineralocorticoid receptors in living cells:: Effects of receptor agonists and antagonists [J].
Fejes-Tóth, G ;
Pearce, D ;
Náray-Fejes-Tóth, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (06) :2973-2978
[10]   Trafficking of the androgen receptor in living cells with fused green fluorescent protein-androgen receptor [J].
Georget, V ;
Lobaccaro, JM ;
Terouanne, B ;
Mangeat, P ;
Nicolas, JC ;
Sultan, C .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1997, 129 (01) :17-26