title: LEF1 identifies androgen-independent epithelium in the developing prostate.
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.
authors.affiliation: Department of Urology, New York University School of Medicine, 423 East 23rd Street, New York, New York 10010, USA.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wu
authors.forename: Garrett
authors.initials: G
authors.lastname: Daniels
authors.forename: Ellen
authors.initials: E
authors.lastname: Shapiro
authors.forename: Kun
authors.initials: K
authors.lastname: Xu
authors.forename: Hongying
authors.initials: H
authors.lastname: Huang
authors.forename: Yirong
authors.initials: Y
authors.lastname: Li
authors.forename: Susan
authors.initials: S
authors.lastname: Logan
authors.forename: M Alba
authors.initials: MA
authors.lastname: Greco
authors.forename: Yi
authors.initials: Y
authors.lastname: Peng
authors.forename: Marie E
authors.initials: ME
authors.lastname: Monaco
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.forename: Herbert
authors.initials: H
authors.lastname: Lepor
authors.forename: Irina
authors.initials: I
authors.lastname: Grishina
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D053530:Keratins, Type I / Q000378:metabolism; D053531:Keratins, Type II / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D011467:Prostate / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: C081876:CKAP4 protein, human; D053530:Keratins, Type I; D053531:Keratins, Type II; D019394:Ki-67 Antigen; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D011944:Receptors, Androgen; D051153:Wnt Proteins; D001616:beta-Galactosidase