LEF1 identifies androgen-independent epithelium in the developing prostate

Xinyu Wu, Garrett Daniels, Ellen Shapiro, Kun Xu, Hongying Huang, Yirong Li, Susan Logan, M. Alba Greco, Yi Peng, Marie E. Monaco, Jonathan Melamed, Herbert Lepor, Irina Grishina, Peng Lee

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17 Scopus citations

Abstract

Lymphoid enhancer-binding factor (LEF)1 is a major mediator and a target in canonical Wnt/β-catenin pathway. Interactions between the androgen receptor (AR) and canonical Wnt pathways have been implicated in the development of the genitourinary organs. Here, we investigated the localization and role of LEF1-positive cells during development of the prostate gland in human and in the murine model. We show that during human prostate development, LEF1 is restricted to the basal epithelial layer of the urogenital sinus. During mouse development, Lef1 is also present in the urogenital mesenchyme in addition to the basal epithelial layer of the urogenital sinus. In the course of elongation and branching of the prostatic ducts, Lef1 is localized to the proliferating epithelium at the distal tips of the buds. Notably, during branching morphogenesis, domains of Lef1 and AR are mutually exclusive. We further employed the TOPGAL reporter strain to examine the dynamics of Wnt signaling in the context of prostate regression upon a 7-d treatment with a competitive AR inhibitor, bicaluta-mide. We found that Wnt/Lef1-positive basal cells are not dependent upon androgen for survival. Furthermore, upon bicalutamide treatment, Wnt/Lef1-positive basal progenitors repopulated the luminal compartment. We conclude that Wnt/Lef1 activity identifies an androgen-independent population of prostate progenitors, which is important for embryonic development and organ maintenance and regeneration in the adult. (Molecular Endocrinology 25: 1018-1026, 2011).

Original languageEnglish (US)
Pages (from-to)1018-1026
Number of pages9
JournalMolecular Endocrinology
Volume25
Issue number6
DOIs
Publication statusPublished - Jun 1 2011

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Keywords

  • Ligands: Dihydrotestosterone Testosterone Bicalutamide
  • NURSA Molecule Pages: Nuclear Receptors: AR

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Wu, X., Daniels, G., Shapiro, E., Xu, K., Huang, H., Li, Y., ... Lee, P. (2011). LEF1 identifies androgen-independent epithelium in the developing prostate. Molecular Endocrinology, 25(6), 1018-1026. https://doi.org/10.1210/me.2010-0513