Systematic Analysis of the Functional Relevance of Nuclear Structure and Mechanics in Breast Cancer Progression
Abstract
Due to the PI s move from Brigham and Women s Hospital to Cornell University on July 1, 2011, no research was conducted at Brigham and Women s Hospital during the report period (July 1 Dec 31, 2011). Nonetheless, while waiting for the award transfer to be completed (the official project period start date at Cornell was Feb 1, 2012), we already accomplished several goals of the proposed statement of work. We created panels of cell lines based on two model systems (MCF10A normal epithelial cells; MDA-MB-231 metastatic breast cancer cells) with systematic alterations in the expression of lamins A, B1, B2, C, and lamin B receptor (LBR). We then evaluated the effect of altered lamin expression on nuclear stiffness in these cell lines. While increased expression of lamin A caused stiffer, less deformable nuclei, reduction of lamins A/C expression by shRNA reduced nuclear stiffness. The effect of alterations in other lamins was less substantial. However, expression of LBR resulted in increased lobulation of the nucleus. These preliminary data support our hypothesis that changes in expression of nuclear envelope proteins recently reported in breast cancer is sufficient to cause altered nuclear morphology and stiffness, which could result in altered migration and invasion.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2012
- Accession Number
- ADA565036
Entities
People
- Jan Lammerding
Organizations
- Cornell University