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 human breast epithelial cell line (Sl) that differentiate into acini in the presence of exogenous extracellular matrix, we have identified earlier a link between the nuclear organization of the protein NuMA and the regulation of matrix proteases. We have now engineered cDNA constructs coding for a putative histone-binding sequence (HBS) in NuMA that may play a role in the regulation of matrix proteases. As expected, over-expression of HBS restricted to the cytoplasm of Sl acinar cells doesn't affect BM maintenance. We are now studying the effect of intranuclear HBS on acini. We have also expressed and purified a poly-His- HBS fusion peptide to be used as bait to identify HBS binding partners. Most interestingly both the fusion peptide and the transgene expressed in Si cells seem to oligomerize. This raises the possibility that UBS may act as either a monomer or a dimer depending on the differentiation status and this may regulate its interaction with potential binding partners.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396493
Entities
People
- Sophie A. Leievre
Organizations
- University of California, Berkeley