A microarray-based, integrated approach to identify novel regulators of cancer drug response and apoptosis

Brachat, Arndt and Pierrat, Benoit and Xynos, Alexandros and Brecht, Karin and Simonen, Marjo and Brüngger, Adrian and Heim, Jutta. (2002) A microarray-based, integrated approach to identify novel regulators of cancer drug response and apoptosis. Oncogene, 21 (54). pp. 8361-8371.

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Official URL: https://edoc.unibas.ch/71664/

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DNA microarrays are powerful tools for the analysis of gene expression on a genomic scale. The importance of individual regulatory events for the process under study can however not be deduced unequivocally without additional experiments. We devised a strategy to identify central regulators of cancer drug responses by combining the results of microarray experiments with efficient methods for phenotypic testing of candidate genes. We exposed murine FL5.12 pro-B cells to cisplatin, camptothecin, methotrexate or paclitaxel, respectively and analysed the patterns of gene expression with cDNA microarrays. Drug-specific regulatory events as well as intersections between different apoptotic pathways, including previously studied responses to staurosporine and interleukin-3 (IL-3) deprivation, were identified. Genes shared by at least three pathways were chosen for further analysis. Ectopic expression of three such genes, TEAP, GP49B, and Lipin1 was found to have an anti-proliferative effect on pro-B cells. Interestingly, we identified hemoglobin alpha as a strong pro-apoptotic regulator. While hemoglobin-expressing cells were growing normally in the presence of IL-3, they displayed accelerated apoptosis with similar kinetics as Bax overexpressing cells upon IL-3 removal. The pro-apoptotic effect of hemoglobin was suppressed by Bcl-2 and was characterized by enhanced stimulation of caspase activity.
Faculties and Departments:05 Faculty of Science
UniBasel Contributors:Brecht Brüngger, Karin and Heim, Jutta
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Aug 2019 07:17
Deposited On:20 Aug 2019 07:17

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