title: Scribble is required for pregnancy-induced alveologenesis in the adult mammary gland.
abstract: The cell polarity protein scribble (SCRIB) is a crucial regulator of polarization, cell migration and tumorigenesis. Whereas SCRIB is known to regulate early stages of mouse mammary gland development, its function in the adult gland is not known. Using an inducible RNA interference (RNAi) mouse model for downregulating SCRIB expression, we report an unexpected role for SCRIB as a positive regulator of cell proliferation during pregnancy-associated mammary alveologenesis. SCRIB was required in the epithelial cell compartment of the mammary gland. Lack of SCRIB attenuated prolactin-induced activation of the JAK2-STAT5 signaling pathway. In addition, loss of SCRIB resulted in the downregulation of prolactin receptor (PRLR) at cell surface and its accumulation in intracellular structures that express markers of the Golgi complex and the recycling endosome. Unlike its role in virgin gland as a negative regulator cell proliferation, SCRIB is a positive regulator of mammary epithelial cell proliferation during pregnancy.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 1L7, Canada.
authors.forename: Leena
authors.initials: L
authors.lastname: Baker
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, M5G 2M9, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: BeGora
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, M5G 2M9, Canada.
authors.forename: Faith
authors.initials: F
authors.lastname: Au Yeung
authors.affiliation: Cold Spring Harbor Laboratory, Watson School of Biological Sciences, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Feigin
authors.affiliation: Cold Spring Harbor Laboratory, Watson School of Biological Sciences, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
authors.forename: Avi Z
authors.initials: AZ
authors.lastname: Rosenberg
authors.affiliation: Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Lowe
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 1L7, Canada Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, M5G 2M9, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kislinger
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 1L7, Canada Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, M5G 2M9, Canada Department of Medicine, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, MA 02215, USA smuthusw@bidmc.harvard.edu.
authors.forename: Senthil K
authors.identifier: 0000-0001-6564-9634
authors.initials: SK
authors.lastname: Muthuswamy
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D038081:Organogenesis / Q000187:drug effects; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology; D011981:Receptors, Prolactin / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D053614:Janus Kinase 2; D011388:Prolactin; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; C508433:scrib protein, mouse; C507926:Jak2 protein, mouse
keywords: Mammary alveologenesis; Proliferation; Scribble