How Does Nuclear Organization Maintain Normal Mammary Phenotype
Abstract
Matrix protease-mediated degradation of the basement membrane (BM) surrounding breast epithelial units (acini) is associated with tumor progression. It is critical to understand the molecular mechanisms that underlie the maintenance of an intact BM in order to develop anti-cancer strategies. Using a nonmalignant human breast epithelial cell line (sl) that differentiate into acini in the presence of extracellular matrix, we have identified earlier a link between the nuclear organization of the protein NuMA, via its C-terminus, and cell phenotype, notably matrix protease expression. We have expressed and purified the NuMA C-terminal histone-fold peptide that may be involved in the regulation of matrix proteases. Using this sequence as bait we have pulled down a 65 kDa ligand in nonmalignant cells but not in tumor cells. The histone-fold sequence has also been expressed in Sl cells and the resulting phenotype is being analyzed. We have identified a CH-actin binding domain at the N-terminus of NuMA that may be responsible for the protein anchorage to the cytoskeleton. We have also demonstrated that NuMA shuttles between nucleus and cytoplasm. Altogether our data suggest that NuMA may regulate cell phenotype not only by binding different c-terminus ligands but also by traveling between nucleus and cytoplasm.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408754
Entities
People
- Sophie A Lelièvre
Organizations
- University of California, Berkeley