Tumor necrosis factor-alpha related gene response to Epothilone B in ovarian cancer.

Khabele D, Lopez-Jones M, Yang W, Arango D, Gross SJ, Augenlicht LH, Goldberg GL
Gynecol Oncol. 2004 93 (1): 19-26

PMID: 15047209 · DOI:10.1016/j.ygyno.2003.11.058

OBJECTIVES - Epothilone B (EpoB) is a non-taxane microtubule-stabilizing agent with a mode of action similar to that of paclitaxel, but with the advantage of being active in paclitaxel-resistant cells. Knowledge regarding other mechanisms of EpoB action is limited. The purpose of this study was to identify gene expression profiles associated with the biological response to EpoB in an ovarian cancer cell line (SKOV3).

METHODS - SKOV3 cells were maintained in McCoy's 5A media. Equal densities cells were treated with or without EpoB, and were evaluated for cell growth arrest and apoptosis. mRNA expression was evaluated by cDNA microarrays and quantitative, real time reverse transcription polymerase chain reaction (QRTPCR).

RESULTS - EpoB (10 nM) led to cell cycle arrest and apoptosis in SKOV3 cells. Microarray analysis, comparing EpoB-treated to untreated cells, revealed altered expression of 41 genes. There was a predominance of sequences related to the TNFalpha stress response pathway. Differential expression of selected genes was confirmed by QRTPCR.

CONCLUSIONS - We demonstrated that cDNA microarrays are a useful tool to rapidly screen for patterns of gene expression that characterize drug response. The microarray data suggest that the microtubule-stabilizing agent, EpoB, triggers stress-related signal transduction pathways related to TNFalpha. These pathways may contribute to mechanisms of EpoB action and potential mechanisms of resistance in ovarian cancer.

MeSH Terms (19)

Antineoplastic Agents Apoptosis Cell Line, Tumor Epothilones Female Flow Cytometry Fluorescent Antibody Technique G2 Phase Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Metallothionein Mitosis Oligonucleotide Array Sequence Analysis Ovarian Neoplasms Tetrazolium Salts Thiazoles Tumor Necrosis Factor-alpha Up-Regulation

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