The Role of Mitotic Events in Taxol Mediated apoptosis in Breast Cancer Cells
Abstract
For a drug that is used so widely in breast cancer therapy, little is known about the mechanism of Taxol action. Although Taxol's binding to tubulin is well characterized and the ability of the drug to induce a mitotic arrest is recognized, the biochemical mechanisms by which these events lead to breast cancer cell cytotoxicity are not known. The objective of this research is to test the hypothesis that prolonged activation of Cdc2 and subsequent phosphorylation of Bcl2 are required for Taxol-mediated apoptosis in breast cancer cells. The ultimate goal of the research is to identify a signaling cascade(s) that is important for the cytotoxic effects of Taxol. Progress to date includes: (i) development of cell model systems to analyze the role of Bcl2 phosphorylation in susceptibility to Taxol-mediated apoptosis; (ii) determining that Bcl2 overexpression provides a selective advantage for cell survival and growth in anchorage-independent settings in vitro and in vivo; and (iii) preliminary confirmation that Taxol-induced modulation of mitotic events that is observed in cell culture models is operational in vivo. It is critical to understand how Taxol works at the molecular level in order to pursue rational design of new drugs for the treatment of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2001
- Accession Number
- ADA403689
Entities
People
- Jennifer A. Pietenpol
Organizations
- Vanderbilt University Medical Center