title: Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers.
abstract: Taxanes such as docetaxel belong to a group of microtubule-targeting agents (MTAs) that are commonly relied upon to treat cancer. However, taxane resistance in cancerous cells drastically reduces the effectiveness of the drugs' long-term usage. Accumulated evidence suggests that the mechanisms underlying taxane resistance include both general mechanisms, such as the development of multidrug resistance due to the overexpression of drug-efflux proteins, and taxane-specific mechanisms, such as those that involve microtubule dynamics. Because taxanes target cell microtubules, measuring microtubule dynamic instability is an important step in determining the mechanisms of taxane resistance and provides insight into how to overcome this resistance. In the experiment, an in vivo method was used to measure microtubule dynamic instability. GFP-tagged α-tubulin was expressed and incorporated into microtubules in MCF-7 cells, allowing for the recording of the microtubule dynamics by time lapse using a sensitive camera. The results showed that, as opposed to the non-resistant parental MCF-7CC cells, the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitive to docetaxel treatment, which causes the resistance to docetaxel-induced mitotic arrest and apoptosis. This paper will outline this in vivo method of measuring microtubule dynamic instability.
authors.affiliation: Department of Medical Genetics, Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta.
authors.forename: Richard
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta.
authors.forename: Harris
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics, Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta; zhixiang.wang@ualberta.ca.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D003952:Diagnostic Imaging / Q000379:methods*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008870:Microtubules; D043823:Taxoids / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel; C080625:taxane