Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

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 Î³-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 Î³-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. Cells were exposed to 8Gy and gene expression ratios between untreated (Cy5) cells and exposed cells (Cy3) were measured four hours later

ORGANISM(S): Homo sapiens

SUBMITTER: Sally Amundson

PROVIDER: E-GEOD-7505 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Integrating global gene expression and radiation survival parameters across the 60 cell lines of the National Cancer Institute Anticancer Drug Screen.

Amundson Sally A SA Do Khanh T KT Vinikoor Lisa C LC Lee R Anthony RA Koch-Paiz Christine A CA Ahn Jaeyong J Reimers Mark M Chen Yidong Y Scudiero Dominic A DA Weinstein John N JN Trent Jeffrey M JM Bittner Michael L ML Meltzer Paul S PS Fornace Albert J AJ

Cancer research 20080101 2

The 60 cell lines of the National Cancer Institute Anticancer Drug Screen (NCI-60) constitute the most extensively characterized in vitro cancer cell model. They have been tested for sensitivity to more than 100,000 potential chemotherapy agents and have been profiled extensively at the DNA, RNA, protein, functional, and pharmacologic levels. We have used the NCI-60 cell lines and three additional lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonoge ...[more]

PMID: 18199535

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Project description:The growing number of particle treatment facilities worldwide and patients treated with particles instead of X-rays marks the upcoming rearrangement of modern radiotherapy. Especially for tumors being difficult to access and for tumors that are resistant to conventional X-ray treatment particle radiotherapy is a beneficial technology. At the Heidelberg Ion Beam Therapy Center (HIT) patients are treated with this technology since 2009 as it offers clear benefits. Contrary to X-rays, which show an exponential dose decrease (after reaching electron equilibrium) with increasing tissue depth, charged particles deposit most of their energy to a small region within the tissue with a sharp dose fall-off after the so-called Bragg peak. This precise dose localization enables further dose escalation within the tumor while sparing healthy tissue. Besides physical advantages, particle radiotherapy offers additional biological advantages. In radiobiology, the term relative-biological effectiveness (RBE) is defined as the ratio of X-rays dose to an alternative irradiation modality dose which produce the same biological effect (e.g. survival or number of DSBs). While protons have a relative biological effectiveness (RBE) comparable to X-rays, carbon ions are more effective in inducing DNA damage(1, 2) and are therefore especially useful for radioresistant tumors. This is due to the fact, that carbon ions induce clustered and direct DNA damage, which is considered to be less dependent on cell cycle stage, oxygen level, genetic background and hinders DNA repair mechanisms(3–6). Nevertheless, their exact mode of action and cellular mechanisms are largely unknown. We show the first comprehensive proteomic and phosphoproteomic study elucidating the cellular response to treatment with protons, carbon ions and X-rays. We found that 2h after treatment with these radiations negligible regulation occurred at protein expression level. But 181 phosphorylation sites were deregulated by ionizing radiation contributing mainly to DNA damage response functionalities. Interestingly we found 55 phosphorylation sites being differentially regulated between the radiations. Here, we observed protons and carbon ions producing equal cellular response whereas X-rays show altered regulation for certain phosphorylation sites. A subset of 28 phosphorylation sites being involved in the DNA damage response or differentially regulated between the ionizing radiations was selected for result confirmation.

Dataset Information

Microarray profiles of radiation response in the NCI60 cell lines

Publications

Integrating global gene expression and radiation survival parameters across the 60 cell lines of the National Cancer Institute Anticancer Drug Screen.

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