rdf-syntax-grammar
mods:
  schema location: http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
  title info:
    title: Regulation of mammary lactogenic differentiation by singleminded-2s
  name:
    name part: Wellberg, Elizabeth.
    role:
      role term: creator
  name:
    name part: Porter, Weston W.
    role:
      role term: thesis advisor.
  type of resource: text
  genre: bibliography
  origin info:
    place:
      place term: txu
    date issued: 2010
    issuance: monographic
  language:
    language term: eng
  physical description:
    form: remote
    extent: 1 online resource.
  abstract: Sim2s is a basic helix-loop-helix Per-Arnt-Sim (bHLH-PAS) transcription factor. In Drosophila, the Sim2 homolog, sim, is necessary for cell fate determination during central nervous system (CNS) development. In mammals, both Sim2 isoforms are involved in development of various tissues, including muscle, cartilage, and mammary gland. Loss-of-function studies revealed a role for Sim2s in specifying epithelial cell fate during mammary development and inhibiting growth and invasion of aggressive breast cancer cells. This study determined the role of Sim2s in mammary epithelial cell differentiation. Our hypothesis is that Sim2s is sufficient to promote lactogenic differentiation in vivo, characterized by expression of lactation-specific genes. Two models were used to test this hypothesis: (1) a transgenic mouse, expressing Sim2s under control of the MMTV-LTR, and (2) the mouse mammary epithelial cell line HC11. Together, these models allow analysis of the effect of Sim2s on global mammary gland differentiation and the mechanism through which it accomplishes this in a relatively homogenous population of cells. We determined that precocious expression of Sim2s in vivo is associated with upregulation of a subset of milk protein genes in nulliparous females. During early pregnancy, Sim2s regulation of lactogenic differentiation extended to a larger group of genes. Following pup removal, Sim2s appears to promote survival of alveolar epithelial cells. In vitro, Sim2s expression is necessary for maximal Csn2 expression, as determined by loss-of-function studies. Overexpression of Sim2s is sufficient to enhance prolactin-mediated Csn2 expression. Chromatin immunoprecipitation assays performed in HC11 cells revealed enhanced recruitment of Stat5a and RNA Polymerase II (RNAPII) to the regulatory region of Csn2 in the presence of Sim2s. In addition, Sim2s and RNAPII were found in a complex that was localized to both the promoter and coding region of the Csn2 gene. These studies sup…
  note: by Elizabeth Wellberg.
  note: "Major Subject: Toxicology"
  note: Title from author supplied metadata (automated record created 2010-08-20 08:31:34).
  note: Electronic resource.
  note: Doctor of Philosophy Texas A&M University 2009 http://hdl.handle.net/1969.1/ETD-TAMU-2009-05-381
  note: Includes bibliographical references.
  note: Text (Dissertation)
  subject:
    topic: Major toxicology
  subject:
    topic: cellular differentiation
  subject:
    topic: mammary gland
  subject:
    topic: Singleminded-2s
  identifier: http://hdl.handle.net/1969.1/ETD-TAMU-2009-05-381
  record info:
    record content source: TXA
    record creation date: 100902
    record change date: 20151201154946.0
    record identifier: in00002601345