title: Wnt/β-Catenin-Responsive Cells in Prostatic Development and Regeneration.
abstract: The precise role of Wnt/β-catenin signaling during prostatic development and tumorigenesis is unclear. Axin2 is a direct transcriptional target of β-catenin. Recent studies have shown that Axin2-expressing cells have stem/progenitor cell properties in a variety of mouse tissues. Here, we genetically labeled Axin2-expressing cells at various time points and tracked their cellular behavior at different developmental and mature stages. We found that prostatic Axin2-expressing cells mainly express luminal epithelial cell markers and are able to expand luminal cell lineages during prostatic development and maturation. They can also survive androgen withdrawal and regenerate prostatic luminal epithelial cells following androgen replacement. Deletion of β-catenin or expression of stabilized β-catenin in these Axin2-expressing cells results in abnormal development or oncogenic transformation, respectively. Our study uncovers a critical role of Wnt/β-catenin-responsive cells in prostatic development and regeneration, and that dysregulation of Wnt/β-catenin signaling in these cells contributes to prostatic developmental defects and tumorigenesis.
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Suk Hyung
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Johnson
authors.affiliation: Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Luong
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Yu
authors.affiliation: Department of Urology, School of Medicine, University of California San Francisco, San Francisco, California, USA.
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Cunha
authors.affiliation: Department of Developmental Biology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Roel
authors.initials: R
authors.lastname: Nusse
authors.affiliation: Department of Urology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Zijie
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000096:biosynthesis*; D019070:Cell Lineage; D004847:Epithelial Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D038081:Organogenesis / Q000502:physiology; D011467:Prostate / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000096:biosynthesis*
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse; D051176:beta Catenin
keywords: Axin2; Prostatic progenitor cells; Wnt signaling; β-Catenin