Gene Expression Profiling of Epothilone A-resistant Cells

Peter Atadja, Yan Yan-Neale, Harry Towbin, Frank Buxton, Dalia Cohen

Novartis Found Symp. 2002;243:119-32; discussion 132-6, 180-5.

PMID: 11990772

Abstract:

In the current study, we isolated sublines of the human breast adenocarcinoma cell line MDA 435 that exhibited increasing resistance to epothilone A, a microtubule-stabilizing cytotoxic agent. The resistant cells did not express P glycoprotein or multidrug resistance-associated protein (MRP) which are known mediators of multidrug resistance (MDR). Two groups of epothilone A-resistant cells were selected: cells which exhibited low resistance to both epothilone A and Taxol, and cells which exhibit low resistance to Taxol but high resistance to epothilone A. cDNA microarrays of epothilone A-resistant and Taxol-resistant cells were utilized to further characterize epothilone A resistance. Hierarchical clustering of genes according to their levels of expression indicated that the majority of genes which were highly expressed in epothilone A-resistant cells but not in taxol-resistant MDR cells encode known interferon-inducible proteins. Genes whose expression increased with increasing epothilone A resistance include microtubule-associated GTPases, cytoskeletal proteins, cell signalling proteins and a drug metabolising enzyme. The majority of the genes that were repressed in both epothilone A- and Taxol-resistant cells encode proteins regulating cellular growth signalling mechanisms.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP152044536	(−)-Epothilone A		152044-53-6	Price

Catalog Number

Product Name

Structure

CAS Number

Price

AP152044536

(−)-Epothilone A

152044-53-6

Price

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