Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/27419
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Title

Daunorubicin-induced variations in gene transcription: commitment to proliferation arrest, senescence and apoptosis

AuthorsMansilla, Sylvia CSIC ORCID; Piña, Benjamín CSIC ORCID ; Portugal, José CSIC ORCID
KeywordsAnthracyclines
Array
Cell cycle
Jurkat T lymphocyte
Transcriptome
Issue Date15-Jun-2003
PublisherPortland Press
CitationBiochemical Journal 372(3): 703-711 (2003)
AbstractWe used a human cDNA macroarray containing various oncogenes and tumour suppressor genes to assess gene expression profiles in early-passage Jurkat T lymphocytes treated with clinically relevant concentrations of the antitumour antibiotic daunorubicin. Several oncogenes and tumour suppressor genes were either up- or down-regulated depending on the daunorubicin concentration used. The expression levels of some of these genes were confirmed by semi-quantitative reverse transcriptase-PCR. We also compared the changes in cell-cycle distribution and the apoptotic morphological characteristics of the cells treated with daunorubicin, using flow cytometry and fluorescence microscopy. Exposure to 182 nM daunorubicin (its IC(75) in Jurkat T cells: where IC(75) is the drug concentration that inhibits growth by 75%) resulted in cell-cycle arrest in G(1) and almost immediate apoptosis. In contrast, decreasing the drug concentration to 91 nM (close to the IC(50)) caused G(2) arrest and cell senescence-like growth arrest, whereas features of apoptosis and necrosis appeared only after longer incubation times. Gene expression profiles, cell-cycle distribution, the presence of DNA damage and the time-dependent response of Jurkat T cells to cell death were correlated clearly. The general behaviour of the genes suggests that cell-cycle arrest and cell death follow distinct pathways depending on drug concentration.
Description9 pages, 6 figures, 2 tables.-- PMID: 12656675 [PubMed].-- PMCID: PMC1223450.
Publisher version (URL)http://dx.doi.org/10.1042/BJ20021950
URIhttp://hdl.handle.net/10261/27419
DOI10.1042/BJ20021950
ISSN0264-6021
E-ISSN1470-8728
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