The Use of a Human Breast Tumor Progression Series and a 3-D Culture Model to Determine if Nuclear Structure Could Provide a Molecular and Therapeutic Marker

Abstract

Alteration in nuclear organization is a hallmark of cancer cells. Nuclear organization is likely to be dependent on the arrangement of a non chromatin structure, referred to as the nuclear matrix (NM). An increasing number of key proteins have been identified as NM proteins, however, the role played by their organization in the regulation of nuclear function and cell phenotype remains unknown. Using a model of human mammary epithelial cell (HMEC) morphogenesis and tumorigenesis, I have found that the NM protein NuMA progressively redistributes in the nucleus during morphogenesis, to ultimately form large domains that co-localize with splicing factors. Such changes are not observed in tumor cells cultured in the same conditions. Moreover, alteration of the supramolecular organization of NuMA in cells that have undergone morphogenesis, induces changes in chromatin structure and alterations in cellular phenotype. This demonstrates that the supramolecular organization of NuMA regulates the maintenance of HMEC differentiation.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 1998
Accession Number
ADB248428

Entities

People

  • Sophie A Lelièvre

Organizations

  • University of California, Berkeley

Tags

DTIC Thesaurus Topics

  • Biological Sciences
  • Breast Cancer
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemistry
  • Cytoskeleton
  • Enzyme Inhibitors
  • Epithelial Cells
  • Genetics
  • Growth Factors
  • Intercellular Junctions
  • Intranuclear Space
  • Proteins
  • Three Dimensional
  • Two Dimensional

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics