Taxol Resistance and Microtubule Dynamics in Breast Cancer
Annual rept. 15 May 2002-14 May 2003
ALBERT EINSTEIN COLL OF MEDICINE OF (YESHIVA UNIV) BRONX NY
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Alterations to microtubule dynamics, leading to a less stable polymer, may be a crucial determinant in the development of resistance towards Taxol, and other drugs with a binding site on the microtubule polymer. We propose that two potential mechanisms by which breast cancer cells could alter their microtubule dynamics are by 1 differential expression of the several a and B tubulin isforms and 2 differential binding of endogenous regulators of microtubule assembly to the cytoskeleton as a result of posttranslational modifications to these tubulin isoforms. The overall goal of this proposal is to develop rapid and innovative protein-based technologies for both quantitating the alpha- and Beta-tubulin isoform composition in drug-sensitive and -resistant human breast cell lines, and for characterizing the posttranslational modifications to these isoforms. It is only by thoroughly understanding Taxol resistance in human breast cancer cells that we will be able to develop ways to overcome Taxol resistance in breast cancer.
- Anatomy and Physiology
- Medicine and Medical Research