Matrix Metalloproteinase Stromelysin-1 Triggers a Cascade of Molecular Alterations that leads to stable epithelial-to-Mesenchymal Conversion and a Premalignant Phenotype in Mammary Epithelial Cells Metadata

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Title

  • Main Title Matrix Metalloproteinase Stromelysin-1 Triggers a Cascade of Molecular Alterations that leads to stable epithelial-to-Mesenchymal Conversion and a Premalignant Phenotype in Mammary Epithelial Cells

Creator

  • Author: Lochter, A.
    Creator Type: Personal
  • Author: Galosy, S.
    Creator Type: Personal
  • Author: Muschler, J.
    Creator Type: Personal
  • Author: Freedman, N.
    Creator Type: Personal
  • Author: Werb, Z.
    Creator Type: Personal
  • Author: Bissell, M.J.
    Creator Type: Personal

Contributor

  • Sponsor: Life Sciences Division
    Contributor Type: Organization

Publisher

  • Name: Lawrence Berkeley National Laboratory
    Place of Publication: Berkeley, California
    Additional Info: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (United States)

Date

  • Creation: 1997-08-11

Language

  • English

Description

  • Content Description: Matrix metalloproteinases (MMPs) regulate ductal morphogenesis, apoptosis, and neoplastic progression in mammary epithelial cells. To elucidate the direct effects of MMPs on mammary epithelium, we generated functionally normal cells expressing an inducible autoactivating stromelysin-1 (SL-1) transgene. Induction of SL-1 expression resulted in cleavage of E-cadherin, and triggered progressive phenotypic conversion characterized by disappearance of E-cadherin and catenins from cell-cell contacts, downregulation of cytokeratins, upregulation of vimentin, induction of keratinocyte growth factor expression and activation, and upregulation of endogenous MMPs. Cells expressing SL-1 were unable to undergo lactogenic differentiation and became invasive. Once initiated, this phenotypic conversion was essentially stable, and progressed even in the absence of continued SL-1 expression. These observations demonstrate that inappropriate expression of SL-1 initiates a cascade of events that may represent a coordinated program leading to loss of the differentiated epithelial phenotype and gain of some characteristics of tumor cells. Our data provide novel insights into how MMPs function in development and neoplastic conversion.
  • Physical Description: 12

Subject

  • Keyword: Growth Factors
  • Keyword: Epithelium
  • Keyword: Apoptosis
  • Keyword: Tumor Cells
  • Keyword: Morphogenesis
  • STI Subject Categories: 99
  • Keyword: Phenotype
  • Keyword: Cleavage
  • Keyword: Induction

Source

  • Journal Name: Journal of Cell Biology; Journal Volume: 139; Journal Issue: 7; Related Information: Journal Publication Date: 1997

Collection

  • Name: Office of Scientific & Technical Information Technical Reports
    Code: OSTI

Institution

  • Name: UNT Libraries Government Documents Department
    Code: UNTGD

Resource Type

  • Article

Format

  • Text

Identifier

  • Report No.: LBNL-41887
  • Grant Number: DE-AC02-05CH11231
  • Office of Scientific & Technical Information Report Number: 1007188
  • Archival Resource Key: ark:/67531/metadc829363