Gene expression profiling of epothilone A-resistant cells.

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.

• Authors: Peter Atadja, Yan Yan-Neale, Harry Towbin, Frank Buxton, Dalia Cohen
• Journal: Novartis Foundation symposium (Novartis Found Symp) Vol. 243 Pg. 119-32; discussion 132-6, 180-5 ( 2002) ISSN: 1528-2511 [Print] England
• PMID: 11990772 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Cytoskeletal Proteins
• Epothilones
• Growth Substances
• Neoplasm Proteins
• epothilone A
• Interferons
• GTP Phosphohydrolases
• Paclitaxel
• epothilone B

Topics

• Adenocarcinoma (genetics, pathology)
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (genetics, pathology)
• Cytoskeletal Proteins (biosynthesis, genetics)
• Drug Resistance, Neoplasm (genetics)
• Epothilones (pharmacology)
• Female
• GTP Phosphohydrolases (biosynthesis, genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Growth Substances (biosynthesis, genetics)
• HL-60 Cells (drug effects)
• Humans
• Interferons (pharmacology)
• Male
• Microtubules (drug effects)
• Neoplasm Proteins (biosynthesis, genetics, physiology)
• Paclitaxel (pharmacology)
• Tumor Cells, Cultured (drug effects, metabolism)