title: The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells.
abstract: Activation of Wnt/β-catenin signaling in adult mouse epidermis leads to expansion of the stem cell compartment and redirects keratinocytes in the interfollicular epidermis and sebaceous glands (SGs) to differentiate along the hair follicle (HF) lineages. Here we demonstrate that during epidermal development and homeostasis there is reciprocal activation of the androgen receptor (AR) and β-catenin in cells of the HF bulb. AR activation reduced β-catenin-dependent transcription, blocked β-catenin-induced induction of HF growth, and prevented β-catenin-mediated conversion of SGs into HFs. Conversely, AR inhibition enhanced the effects of β-catenin activation, promoting HF proliferation and differentiation, culminating in the formation of benign HF tumors and a complete loss of SG identity. We conclude that AR signaling has a key role in epidermal stem cell fate selection by modulating responses to β-catenin in adult mouse skin.
authors.affiliation: Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital Campus, London, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.
authors.forename: Kai
authors.initials: K
authors.lastname: Kretzschmar
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
authors.forename: Denny L
authors.initials: DL
authors.lastname: Cottle
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK; Cancer Research UK Cambridge Research Institute, University of Cambridge, Cambridge, UK.
authors.forename: Pawel J
authors.initials: PJ
authors.lastname: Schweiger
authors.affiliation: Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital Campus, London, UK. Electronic address: fiona.watt@kcl.ac.uk.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Watt
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D018859:Hair Follicle / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000378:metabolism*; D012627:Sebaceous Glands / Q000166:cytology; D012680:Sensitivity and Specificity; D013234:Stem Cells / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D011944:Receptors, Androgen; D051176:beta Catenin