Editors' ChoiceCancer

Androgen Receptor and β-Catenin Linked

Science's STKE  02 Apr 2002:
Vol. 2002, Issue 126, pp. tw124
DOI: 10.1126/stke.2002.126.tw124

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.

F. Yang, X. Li, M. Sharma, C. Y. Sasaki, D. L. Longo, B. Lim, Z. Sun, Linking β-catenin to androgen-signaling pathway. J. Biol. Chem. 277: 11336-11344 (2002). [Full Text] [Abstract]