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Author Lelie'vre, S. A. ♦ Weaver, V. M. ♦ Nickerson, J. A. ♦ Larabell, C. A. ♦ Petersen, O. W. ♦ Bissell, M. J.
Sponsorship Life Sciences Division
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
File Format PDF
Language English
Subject Keyword GENERAL AND MISCELLANEOUS ♦ ACETYLATION ♦ BREAKDOWN ♦ CELL CYCLE ♦ CELL PROLIFERATION ♦ CHROMATIN ♦ DISTRIBUTION ♦ GENES ♦ HISTONES ♦ MEMBRANES ♦ MORPHOGENESIS ♦ NUCLEAR MATRIX ♦ PHENOTYPE ♦ PROTEINS ♦ SPLICING
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 ref lecting changes in gene expression, nuclear organization itself can modulate the cellular and tissue phenotype.
ISSN 00278424
Educational Use Research
Learning Resource Type Article
Publisher Date 1998-08-14
Publisher Place United States
Volume Number 95
Issue Number 25
Technical Publication No. LBNL-42692
Organization Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)


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