Sci. STKE, 2 April 2002
Cancer Androgen Receptor and β-Catenin Linked
β-catenin, best known for its role in Wnt signaling, in which it forms transcriptionally active complexes with members of the Tcf/LEF family, appears to also promote transcription through a specific interaction with the androgen nuclear receptor (AR). That's the conclusion of Yang et al. who picked out β-catenin in a yeast two-hybrid screen modified to detect proteins that showed androgen-dependent interaction with the AR. The authors went on to map the region of interaction in vitro with GST-fusion proteins and to show interaction of the endogenous proteins when immunoprecipitated from the human prostate cancer cell line LNCaP. Overexpression of β-catenin in transfected cells enhanced AR-mediated transcription of a reporter plasmid. β-catenin also functions in cell adhesion through interaction with E-cadherin at the cell membrane. In a prostate cancer cell line that does not express e-cadherin, transfected β-catenin was found in the cytoplasm and nucleus. Transfected E-cadherin caused redistribution of β-catenin to the plasma membrane and reduced AR-activated transcription of a reporter gene. Prostate cancer cells often show androgen-dependint growth, and the authors note that better understanding of the influence of β-catenin on AR signaling may lead to more effective therapies to halt such uncontrolled growth.
Citation: Androgen Receptor and β-Catenin Linked. Sci. STKE 2002, tw124 (2002).
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