Taxol Resistance and Microtubule Dynamics in Breast Cancer

摘要

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 isoforms 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.