CellMiner: a relational database and query tool for the NCI-60 cancer cell lines

Shankavaram, Uma; Varma, Sudhir; Kane, David W.; Sunshine, Margot; Chary, Krishna; Reinhold, William C.; Pommier, ﻿Yves; Weinstein, John N.

doi:10.1186/1471-2164-10-277

Cited by 325 publications

(281 citation statements)

References 24 publications

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“…However, examination of Top2␣ and NF-YB gene expression levels in the National Cancer Institute (NCI)-60 panel of human tumor cancer cell lines (http://discover.nci. nih.gov/cellminer/) (Shankavaram et al, 2009) suggests that there is no significant overall correlation, negative or positive, between Top2␣ and NF-YB at the mRNA level (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

Novel Regulation of Nuclear Factor-YB by miR-485-3p Affects the Expression of DNA Topoisomerase IIα and Drug Responsiveness

Chen¹,

He²,

Arslan³

et al. 2011

Mol Pharmacol

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Nuclear factor (NF)-YB, a subunit of the transcription factor nuclear factor Y (NF-Y) complex, binds and activates CCAATcontaining promoters. Our previous work suggested that NF-YB may be a mediator of topoisomerase II␣ (Top2␣), working through the Top2␣ promoter. DNA topoisomerase II (Top2) is an essential nuclear enzyme and the primary target for several clinically important anticancer drugs. Our teniposide-resistant human lymphoblastic leukemia CEM cells (CEM/VM-1-5) express reduced Top2␣ protein compared with parental CEM cells. To study the regulation of Top2␣ during the development of drug resistance, we found that NF-YB protein expression is increased in CEM/VM-1-5 cells compared with parental CEM cells. This further suggests that increased NF-YB may be a negative regulator of Top2␣ in CEM/VM-1-5 cells. We asked what causes the up-regulation of NF-YB in CEM/VM-1-5 cells.We found by microRNA profiling that hsa-miR-485-3p is lower in CEM/VM-1-5 cells compared with CEM cells. MicroRNA target prediction programs revealed that the 3Ј-untranslated region (3Ј-UTR) of NF-YB harbors a putative hsa-miR-485-3p binding site. We thus hypothesized that hsa-miR-485-3p mediates drug responsiveness by decreasing NF-YB expression, which in turn negatively regulates Top2␣ expression. To test this, we overexpressed miR-485-3p in CEM/VM-1-5 cells and found that this led to reduced expression of NF-YB, a corresponding up-regulation of Top2␣, and increased sensitivity to the Top2 inhibitors. Results in CEM cells were replicated in drug-sensitive and -resistant human rhabdomyosarcoma Rh30 cells, suggesting that our findings represent a general phenomenon. Ours is the first study to show that miR-485-3p mediates Top2␣ down-regulation in part by altered regulation of NF-YB.

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Section: Discussionmentioning

confidence: 99%

Novel Regulation of Nuclear Factor-YB by miR-485-3p Affects the Expression of DNA Topoisomerase IIα and Drug Responsiveness

Chen¹,

He²,

Arslan³

et al. 2011

Mol Pharmacol

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“…Data concerning SLFN11 expression in the ovarian cancer dataset (18) NCI-60 Drug Cytotoxicity Data. In vitro cytotoxicity data were obtained from our database, CellMiner (9,13). In addition, data for 15 recently tested drugs were obtained from the Developmental Therapeutics Program website (10).…”

Section: Methodsmentioning

confidence: 99%

“…We next expanded our correlation analysis to include a total of 1,444 compounds with a known mechanism of action, which have been tested independently in the NCI-60 more than twice (9,12,13). The high positive correlation between SLFN11 expression and cytotoxicity was not limited to Top1 inhibitors, but was also strongly significant for different categories of DDAs (Dataset S2).…”

Section: Slfn11 Expression Correlates With the Antiproliferative Actimentioning

confidence: 99%

“…It has been tested since the 1980s for more than 400,000 compounds of natural and synthetic origin (8)(9)(10). The NCI-60 panel has also been extensively characterized for gene expression using six different microarray platforms (11)(12)(13) and copy-number variation by array-based comparative genomic hydridization (aCGH) (9,14) and has recently been sequenced for the entire exome at the National Cancer Institute (National Institutes of Health).…”

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confidence: 99%

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Putative DNA/RNA helicase Schlafen-11 (SLFN11) sensitizes cancer cells to DNA-damaging agents

Zoppoli

Regairaz

Leo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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DNA-damaging agents (DDAs) constitute the backbone of treatment for most human tumors. Here we used the National Cancer Institute Antitumor Cell Line Panel (the NCI-60) to identify predictors of cancer cell response to topoisomerase I (Top1) inhibitors, a widely used class of DDAs. We assessed the NCI-60 transcriptome using Affymetrix Human Exon 1.0 ST microarrays and correlated the in vitro activity of four Top1 inhibitors with gene expression in the 60 cell lines. A single gene, Schlafen-11 (SLFN11), showed an extremely significant positive correlation with the response not only to Top1 inhibitors, but also to Top2 inhibitors, alkylating agents, and DNA synthesis inhibitors. Using cells with endogenously high and low SLFN11 expression and siRNA-mediated silencing, we show that SLFN11 is causative in determining cell death and cell cycle arrest in response to DDAs in cancer cells from different tissues of origin. We next analyzed SLFN11 expression in ovarian and colorectal cancers and normal corresponding tissues from The Cancer Genome Atlas database and observed that SLFN11 has a wide expression range. We also observed that high SLFN11 expression independently predicts overall survival in a group of ovarian cancer patients treated with cisplatin-containing regimens. We conclude that SLFN11 expression is causally associated with the activity of DDAs in cancer cells, has a broad expression range in colon and ovarian adenocarcinomas, and may behave as a biomarker for prediction of response to DDAs in the clinical setting.

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“…REIMS analysis does not only allow rapid identification of cell lines based on their spectral fingerprint, but opens the way to the detailed characterization of membrane lipid composition in different cancer phenotypes. The correlation between REIMS spectral data and gene and protein expression data can be assessed using publicly available resources such as the CellMiner database 39 which will allow to assess the sensitivity of the REIMS spectral method for tumor phenotypic characterization in detail. In addition, this technique offers a unique possibility to investigate gene knock-out models for changes in lipid metabolism or the effects of feeding experiments with stable isotope-labeled nutrient sources.…”

Section: Resultsmentioning

confidence: 99%

Shotgun Lipidomic Profiling of the NCI60 Cell Line Panel Using Rapid Evaporative Ionization Mass Spectrometry

et al. 2016

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Rapid Evaporative Ionization Mass Spectrometry (REIMS) was used for the rapid mass spectrometric profiling of cancer cell lines. Spectral reproducibility was assessed for three different cell lines and extent of inter-class differences and intraclass variance were found to allow the identification of these cell lines based on the REIMS data. Subsequently, the NCI60 cell line panel was subjected to REIMS analysis and the resulting dataset was investigated for its distinction of individual cell lines and different tissue types of origin. Information content of REIMS spectral profiles of cell lines were found to be similar to those obtained of mammalian tissues although pronounced differences in relative lipid intensity were observed. Ultimately, REIMS was shown to detect changes in lipid content of cell lines due to Mycoplasma infection. The data show that REIMS is an attractive means to study cell lines involving minimal sample preparation and analysis times in the range of seconds.

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CellMiner: a relational database and query tool for the NCI-60 cancer cell lines

Cited by 325 publications

References 24 publications

Novel Regulation of Nuclear Factor-YB by miR-485-3p Affects the Expression of DNA Topoisomerase IIα and Drug Responsiveness

Novel Regulation of Nuclear Factor-YB by miR-485-3p Affects the Expression of DNA Topoisomerase IIα and Drug Responsiveness

Putative DNA/RNA helicase Schlafen-11 (SLFN11) sensitizes cancer cells to DNA-damaging agents

Shotgun Lipidomic Profiling of the NCI60 Cell Line Panel Using Rapid Evaporative Ionization Mass Spectrometry

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