TY - JOUR
T1 - Linking β-catenin to androgen-signaling pathway
AU - Yang, Fajun
AU - Li, Xiaoyu
AU - Sharma, Manju
AU - Sasaki, Carl Y.
AU - Longo, Dan L.
AU - Lim, Bing
AU - Sun, Zijie
PY - 2002/3/29
Y1 - 2002/3/29
N2 - The androgen-signaling pathway is important for the growth and progression of prostate cancer cells. The growth-promoting effects of androgen on prostate cells are mediated mostly through the androgen receptor (AR). There is increasing evidence that transcription activation by AR is mediated through interaction with other cofactors. β-Catenin plays a critical role in embryonic development and tumorigenesis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction. Here, we demonstrate that a specific protein-protein interaction occurs between β-catenin and AR. Unlike the steroid hormone receptor coactivator I (SRC1), β-catenin showed a strong interaction with AR but not with other steroid hormone receptors such as estrogen receptor α, progesterone receptor β, and glucocorticoid receptor. The ligand binding domain of AR and the NH2 terminus combined with the first six armadillo repeats of β-catenin were shown to be necessary for the interaction. Through this specific interaction, β-catenin augments the ligand-dependent activity of AR in prostate cancer cells. Moreover, expression of E-cadherin in E-cadherin-negative prostate cancer cells results in redistribution of the cytoplasmic β-catenin to the cell membrane and reduction of AR-mediated transcription. These data suggest that loss of E-cadherin can elevate the cellular levels of β-catenin in prostate cancer cells, which may directly contribute to invasiveness and a more malignant tumor phenotype by augmenting AR activity during prostate cancer progression.
AB - The androgen-signaling pathway is important for the growth and progression of prostate cancer cells. The growth-promoting effects of androgen on prostate cells are mediated mostly through the androgen receptor (AR). There is increasing evidence that transcription activation by AR is mediated through interaction with other cofactors. β-Catenin plays a critical role in embryonic development and tumorigenesis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction. Here, we demonstrate that a specific protein-protein interaction occurs between β-catenin and AR. Unlike the steroid hormone receptor coactivator I (SRC1), β-catenin showed a strong interaction with AR but not with other steroid hormone receptors such as estrogen receptor α, progesterone receptor β, and glucocorticoid receptor. The ligand binding domain of AR and the NH2 terminus combined with the first six armadillo repeats of β-catenin were shown to be necessary for the interaction. Through this specific interaction, β-catenin augments the ligand-dependent activity of AR in prostate cancer cells. Moreover, expression of E-cadherin in E-cadherin-negative prostate cancer cells results in redistribution of the cytoplasmic β-catenin to the cell membrane and reduction of AR-mediated transcription. These data suggest that loss of E-cadherin can elevate the cellular levels of β-catenin in prostate cancer cells, which may directly contribute to invasiveness and a more malignant tumor phenotype by augmenting AR activity during prostate cancer progression.
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U2 - 10.1074/jbc.M111962200
DO - 10.1074/jbc.M111962200
M3 - Article
C2 - 11792709
AN - SCOPUS:0037192870
SN - 0021-9258
VL - 277
SP - 11336
EP - 11344
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -