How Does Nuclear Organization Maintain Normal Mammary Phenotype?
Abstract
Degradation of the basement membrane (BM) surrounding epithelial units (acini) is associated with tumor progression. It is crucial to understand the molecular mechanisms that underlie the maintenance of an intact BM in order to develop anti-cancer strategies. Using non-neoplastic human breast epithelial S1 cells that differentiate into acini in the presence of extracellular matrix, we have shown a link between the nuclear organization of the protein NuMA, via its C-terminus, and the maintenance of acinar differentiation, notably BM integrity. We have identified a sequence that shares similarities with the histone promoter control 2 (HPC2) protein in the distal portion of the C-terminus of NuMA (NuMA-CTDP). Expression of this sequence in 51 cells prevented acinar differentiation and formation of the BM, and induced a dramatic reorganization of chromatin structure. Fractionation experiments showed that NuMA interacts with the chromatin compartment and suggested that NuMA might be associated with multi-protein complexes. Further sequence analysis of NuMA-CTDP revealed that this region may be restricted to chordates and may adopt a structure possessing organization and signaling properties. Further understanding of the involvement of NuMA in the regulation of chromatin structure is critical to establish whether this protein could become a target for differentiation strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA425883
Entities
People
- Sophie A Lelièvre
Organizations
- University of California, Berkeley