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Open Access 01-12-2014 | Research article

Molecular characterisation of isogenic taxane resistant cell lines identify novel drivers of drug resistance

Authors: Juliet Kenicer, Melanie Spears, Nicola Lyttle, Karen J Taylor, Linda Liao, Carrie A Cunningham, Maryou Lambros, Alan MacKay, Cindy Yao, Jorge Reis-Filho, John MS Bartlett

Published in: BMC Cancer | Issue 1/2014

Abstract

Background

Taxanes such as paclitaxel and docetaxel are used successfully to treat breast cancer, usually in combination with other agents. They interfere with microtubules causing cell cycle arrest; however, the mechanisms underlying the clinical effects of taxanes are yet to be fully elucidated.

Methods

Isogenic paclitaxel resistant (PACR) MDA‒MB‒231, paclitaxel resistant ZR75‒1 and docetaxel resistant (DOCR) ZR75‒1 cell lines were generated by incrementally increasing taxane dose in native cell lines in vitro. We used aCGH analysis to identify mechanisms driving taxane resistance.

Results

Taxane resistant cell lines exhibited an 18-170 fold increased resistance to taxanes, with the ZR75-1 resistant cell lines also demonstrating cross resistance to anthracyclines. Paclitaxel treatment of native cells resulted in a G2/M block and a decrease in the G1 phase of the cell cycle. However, in the resistant cell lines, minimal changes were present. Functional network analysis revealed that the mitotic prometaphase was lost in the resistant cell lines.

Conclusion

This study established a model system for examining taxane resistance and demonstrated that both MDR and mitosis represent common mechanism of taxane resistance.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/762/prepub

Title: Molecular characterisation of isogenic taxane resistant cell lines identify novel drivers of drug resistance
Authors: Juliet Kenicer
Melanie Spears
Nicola Lyttle
Karen J Taylor
Linda Liao
Carrie A Cunningham
Maryou Lambros
Alan MacKay
Cindy Yao
Jorge Reis-Filho
John MS Bartlett
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-14-762

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