Centrosome Defects, Genetic Instability and Breast Cancer Progression
Abstract
Breast cancer is the most prevalent of all cancers and it is the second most common cause of cancer death amongst women. Centrosome defects have been implicated in cancer formation and can be detected very early in this process. The centrosome protein pericentrin is overexpressed in many cancers including breast cancer. We found that down regulation of pericentrin leads to cytokinesis defects and aneuploidy. Pericentrin overexpression leads to an increase in the number of multinucleated cells, suggesting a defect in cytokinesis. In addition to the cytokinesis defects, pericentrin knock down also induce a G0/G1 arrest that is p53-p38 dependent. Moreover, pericentrin knockdown affects cilia formation in epithelial cells. Also, knock down of several other centrosome proteins leads to aG1 arrest and affects cilia formation in epithelial cells. We conclude that pericentrin affects cytokinesis, G1progression and differentiation. Defects during mitosis, as well as loss of checkpoints and uncontrolled cell division are the first steps in cancer formation. Understanding those events will be a major advance in breast cancer research.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA483057
Entities
People
- Stephaine Mirabelle
- Stephen Doxsey
Organizations
- University of Massachusetts Medical School