The Use of a Human Breast Tumor Progression Series and a 3-D Culture Model to Determine if Nuclear Structure Could Provide a Molecular and Therapeutic Marker
Abstract
Alteration in nuclear structure is a hallmark of cancer cells. Nuclear structure partly relies on the supramolecular organization of proteins called nuclear matrix (NM) proteins. By investigating the appearance or disappearance of NM proteins on 2D gels prepared from various stages in a human breast progression series, we have identified potential tumor suppressor or promoter candidates. In addition, using a model of human mammary epithelial cell (HMEC) differentiation and tumorigenesis, we have demonstrated that the NM protein NuMA progressively redistributes within nuclei only during acinar differentiation. Interestingly, cell membrane and NuMA organizations influence each other in acinar cells: Alteration of cell-cell and cell membrane- extracellular matrix (ECM) interactions changes NuMA distribution; conversely, alteration of the supramolecular organization of NuMA abolishes cell membrane-ECM interaction and also induces changes in chromatin structure and increased sensitivity to apoptosis. This indicates that NuMA is a regulator of HMEC differentiation. Moreover, we have developed an imaging algorithm that permits quantitative measurements of differences in NuMA distribution and discrimination between non-malignant and malignant cells even in conditions where the eye cannot separate the staining patterns (e.g., in non-differentiated proliferating cells). These results suggest that the study of NM proteins offers new potentials for anticancer strategies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2000
- Accession Number
- ADB262542
Entities
People
- Mina Bissell
- Sophie A Lelièvre
Organizations
- University of California, Berkeley