TY - JOUR
T1 - LEF1 identifies androgen-independent epithelium in the developing prostate
AU - Wu, Xinyu
AU - Daniels, Garrett
AU - Shapiro, Ellen
AU - Xu, Kun
AU - Huang, Hongying
AU - Li, Yirong
AU - Logan, Susan
AU - Alba Greco, M.
AU - Peng, Yi
AU - Monaco, Marie E.
AU - Melamed, Jonathan
AU - Lepor, Herbert
AU - Grishina, Irina
AU - Lee, Peng
PY - 2011/6
Y1 - 2011/6
N2 - 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).
AB - 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).
KW - Ligands: Dihydrotestosterone Testosterone Bicalutamide
KW - NURSA Molecule Pages: Nuclear Receptors: AR
UR - http://www.scopus.com/inward/record.url?scp=79957733038&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957733038&partnerID=8YFLogxK
U2 - 10.1210/me.2010-0513
DO - 10.1210/me.2010-0513
M3 - Article
C2 - 21527502
AN - SCOPUS:79957733038
SN - 0888-8809
VL - 25
SP - 1018
EP - 1026
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 6
ER -