LEF1 identifies androgen-independent epithelium in the developing prostate |
| |
Authors: | Wu Xinyu Daniels Garrett Shapiro Ellen Xu Kun Huang Hongying Li Yirong Logan Susan Greco M Alba Peng Yi Monaco Marie E Melamed Jonathan Lepor Herbert Grishina Irina Lee Peng |
| |
Institution: | Department of Urology, New York University School of Medicine, 423 East 23rd Street, New York, New York 10010, USA. |
| |
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, bicalutamide. 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|