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Microarray profiles of radiation response in the NCI60 cell lines

ABSTRACT: The 60 cell lines of the NCI Anti-Cancer Drug Screen (NCI60) constitute the most extensively characterized in vitro cancer cell model, and have been tested for sensitivity to over 100,000 potential chemotherapy agents. We have used the NCI60 cell lines and three additional lymphoblast lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis induction, and gene expression response by microarray analysis. While several studies have measured relative basal gene expression in the NCI60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. We found genes differentially regulated in cells with low survival after 2 or 8 Gy γ-rays. In contrast to reported basal gene expression patterns, little tissue-of-origin effect was detected in the radiation response pattern of gene expression, with the exception of lymphoblastoid cell lines. The most striking patterns in the radiation data were a set of genes upregulated preferentially in the p53 wild-type lines, and a set of cell-cycle regulatory genes strongly down-regulated across the entire NCI60 panel. The response of these genes to γ-rays appears to be unaffected by the myriad of genetic differences across this very diverse cell set, and represents the most universal gene expression response to ionizing radiation yet observed. Keywords: radiation response

ORGANISM(S): Homo sapiens

PROVIDER: GSE7505 | GEO | 2008/01/01

SECONDARY ACCESSION(S): PRJNA100479

REPOSITORIES: GEO

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Project description:Biological response X-rays traditionally serves as a standard in comparative analysis of different qualities of ionizing radiation. Most such studies have utilized 2-dimensional culture systems, which may not fully represent responses in 3-dimensional tissues. To gain insight into biological responses to X-rays in tissue, we have profiled global gene expression in EPI-200, a 3-dimensional tissue model that imitates the structure and function of human epidermis, at 4, 16 and 24 hours after exposure to 2.5 Gy of X-rays. The most significant gene ontology groups were associated with cell cycle, cytokinesis, establishment and maintenance of chromatin architecture. Remarkably, genes with a role in cell cycle were predominantly downregulated at all time points while genes involved in the cell defense response - upregulated. Methyltransferases were predominantly upregulated at 4 and 16h while transcription factors - at 16h and 24h suggesting remodeling of the chromatin. Among the genes with a role in signal transduction, irradiation affected kinase modulators and microtubule binding motor proteins at all time points. Kinases, especially non-receptor serine/threonine protein kinases were predominantly upregulated at 16 and 24h suggesting a rearrangement in the signaling pathways. The results also confirm involvement in the biological response of the genes participating in p53 pathway that were overrepresented at 4 and 16h in the set of upregulated genes and ubiquitin proteasome pathway that were predominantly downregulated at 16h and 24h In the same time, growing numbers of altered in expression genes: 449 at 4h; 720 and 3986 genes - at 16 and 24h postirradiation, accordingly suggested that ionizing radiation caused long term changes in the gene expression the exceeded the time frame proposed for this study. Radiation induced gene expression in 3-dimensional tissue model, Epi-200, was measured at 4, 16 and 24 hours after exposure to the dose of 2.5 Gy of X-rays. Three independent experiments were performed in the each time point using one tissue sample per a data point.

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Microarray profiles of radiation response in the NCI60 cell lines

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