Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Tissue Phenotype Depends on Reciprocal Interactions between the Extracellular Matrix and the Structural Organization of the Nucleus

Sophie A. Lelievre, Valerie M. Weaver, Jeffrey A. Nickerson, Carolyn A. Larabell, Ankan Bhaumik, Ole W. Petersen and Mina J. Bissell
Proceedings of the National Academy of Sciences of the United States of America
Vol. 95, No. 25 (Dec. 8, 1998), pp. 14711-14716
Stable URL: http://www.jstor.org/stable/46608
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Tissue Phenotype Depends on Reciprocal Interactions between the Extracellular Matrix and the Structural Organization of the Nucleus
Preview not available

Abstract

What determines the nuclear organization within a cell and whether this organization itself can impose cellular function within a tissue remains unknown. To explore the relationship between nuclear organization and tissue architecture and function, we used a model of human mammary epithelial cell acinar morphogenesis. When cultured within a reconstituted basement membrane (rBM), HMT-3522 cells form polarized and growth-arrested tissue-like acini with a central lumen and deposit an endogenous BM. We show that rBM-induced morphogenesis is accompanied by relocalization of the nuclear matrix proteins NuMA, splicing factor SRm160, and cell cycle regulator Rb. These proteins had distinct distribution patterns specific for proliferation, growth arrest, and acini formation, whereas the distribution of the nuclear lamina protein, lamin B, remained unchanged. NuMA relocalized to foci, which coalesced into larger assemblies as morphogenesis progressed. Perturbation of histone acetylation in the acini by trichostatin A treatment altered chromatin structure, disrupted NuMA foci, and induced cell proliferation. Moreover, treatment of transiently permeabilized acini with a NuMA antibody led to the disruption of NuMA foci, alteration of histone acetylation, activation of metalloproteases, and breakdown of the endogenous BM. These results experimentally demonstrate a dynamic interaction between the extracellular matrix, nuclear organization, and tissue phenotype. They further show that rather than passively reflecting changes in gene expression, nuclear organization itself can modulate the cellular and tissue phenotype.

Page Thumbnails

  • Thumbnail: Page 
14711
    14711
  • Thumbnail: Page 
14712
    14712
  • Thumbnail: Page 
14713
    14713
  • Thumbnail: Page 
14714
    14714
  • Thumbnail: Page 
14715
    14715
  • Thumbnail: Page 
14716
    14716