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MicroRNA profiling of the NCI-60 panel of human cancer cell lines

ABSTRACT: Advances in the understanding of cancer cell biology and response to drug treatment have benefited from new molecular technologies and methods for integrating information from multiple sources. The NCI-60, a panel of 60 diverse human cancer cell lines, has been used by the National Cancer Institute to screen >100,000 chemical compounds and natural product extracts for anticancer activity. The NCI-60 has also been profiled for mRNA and protein expression, mutational status, chromosomal aberrations, and DNA copy number, generating an unparalleled public resource for integrated chemogenomic studies. Recently, microRNAs have been shown to target particular sets of mRNAs, thereby preventing translation or accelerating mRNA turnover. To complement the existing NCI-60 datasets, we have measured expression levels of microRNAs in the NCI-60.

ORGANISM(S): Homo sapiens

SUBMITTER: Blower PE

PROVIDER: S-ECPF-MEXP-1029 | biostudies-other | 2007 May

REPOSITORIES: biostudies-other

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MicroRNA profiling by array of NCI-60 human cancer cell-lines

Project description:Affymetrix GeneChip miRNA arrays were used to profile the expression of microRNAs in cells of sixty NCI-60 cancer cell-lines

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MicroRNA profiling of the NCI-60 panel of human cancer cell lines

Project description:Advances in the understanding of cancer cell biology and response to drug treatment have benefited from new molecular technologies and methods for integrating information from multiple sources. The NCI-60, a panel of 60 diverse human cancer cell lines, has been used by the National Cancer Institute to screen >100,000 chemical compounds and natural product extracts for anticancer activity. The NCI-60 has also been profiled for mRNA and protein expression, mutational status, chromosomal aberrations, and DNA copy number, generating an unparalleled public resource for integrated chemogenomic studies. Recently, microRNAs have been shown to target particular sets of mRNAs, thereby preventing translation or accelerating mRNA turnover. To complement the existing NCI-60 datasets, we have measured expression levels of microRNAs in the NCI-60.

2007-04-02 | E-MEXP-1029 | biostudies-arrayexpress

Transcription profiling of human cell lines from 9 different cancer tissue (NCI-60)

Project description:Comparison between cell lines from 9 different cancer tissue of origin types (Breast, Central Nervous System, Colon, Leukemia, Melanoma, Non-Small Cell Lung, Ovarian, Prostate, Renal) from NCI-60 panel Experiment Overall Design: cell lines from 9 different cancer tissue of origin types

| S-ECPF-GEOD-5949 | biostudies-other

Predicting enzyme targets for cancer drugs by profiling human metabolic reactions in NCI-60 cell lines.

Project description:BackgroundDrugs can influence the whole metabolic system by targeting enzymes which catalyze metabolic reactions. The existence of interactions between drugs and metabolic reactions suggests a potential way to discover drug targets.ResultsIn this paper, we present a computational method to predict new targets for approved anti-cancer drugs by exploring drug-reaction interactions. We construct a Drug-Reaction Network to provide a global view of drug-reaction interactions and drug-pathway interactions. The recent reconstruction of the human metabolic network and development of flux analysis approaches make it possible to predict each metabolic reaction's cell line-specific flux state based on the cell line-specific gene expressions. We first profile each reaction by its flux states in NCI-60 cancer cell lines, and then propose a kernel k-nearest neighbor model to predict related metabolic reactions and enzyme targets for approved cancer drugs. We also integrate the target structure data with reaction flux profiles to predict drug targets and the area under curves can reach 0.92.ConclusionsThe cross validations using the methods with and without metabolic network indicate that the former method is significantly better than the latter. Further experiments show the synergism of reaction flux profiles and target structure for drug target prediction. It also implies the significant contribution of metabolic network to predict drug targets. Finally, we apply our method to predict new reactions and possible enzyme targets for cancer drugs.

| S-EPMC2964682 | biostudies-literature

Transcription profiling of human cell lines from 9 different cancer tissue (NCI-60) (U133 platform)

| S-ECPF-GEOD-5720 | biostudies-other

A map of mobile DNA insertions in the NCI-60 human cancer cell panel.

Project description:BACKGROUND:The National Cancer Institute-60 (NCI-60) cell lines are among the most widely used models of human cancer. They provide a platform to integrate DNA sequence information, epigenetic data, RNA and protein expression, and pharmacologic susceptibilities in studies of cancer cell biology. Genome-wide studies of the complete panel have included exome sequencing, karyotyping, and copy number analyses but have not targeted repetitive sequences. Interspersed repeats derived from mobile DNAs are a significant source of heritable genetic variation, and insertions of active elements can occur somatically in malignancy. METHOD:We used Transposon Insertion Profiling by microarray (TIP-chip) to map Long INterspersed Element-1 (LINE-1, L1) and Alu Short INterspersed Element (SINE) insertions in cancer genes in NCI-60 cells. We focused this discovery effort on annotated Cancer Gene Index loci. RESULTS:We catalogued a total of 749 and 2,100 loci corresponding to candidate LINE-1 and Alu insertion sites, respectively. As expected, these numbers encompass previously known insertions, polymorphisms shared in unrelated tumor cell lines, as well as unique, potentially tumor-specific insertions. We also conducted association analyses relating individual insertions to a variety of cellular phenotypes. CONCLUSIONS:These data provide a resource for investigators with interests in specific cancer gene loci or mobile element insertion effects more broadly. Our data underscore that significant genetic variation in cancer genomes is owed to LINE-1 and Alu retrotransposons. Our findings also indicate that as large numbers of cancer genomes become available, it will be possible to associate individual transposable element insertion variants with molecular and phenotypic features of these malignancies.

| S-EPMC5087121 | biostudies-literature

Expression of microRNAs in the NCI-60 cancer cell-lines.

Project description:The NCI-60 panel of 60 human cancer cell-lines of nine different tissues of origin has been extensively characterized in biological, molecular and pharmacological studies. Analyses of data from such studies have provided valuable information for understanding cellular processes and developing strategies for the diagnosis and treatment of cancer. Here, Affymetrix® GeneChip™ miRNA version 1 oligonucleotide microarrays were used to quantify 847 microRNAs to generate an expression dataset of 495 (58.4%) microRNAs that were identified as expressed in at least one cell-line of the NCI-60 panel. Accuracy of the microRNA measurements was partly confirmed by reverse transcription and polymerase chain reaction assays. Similar to that seen among the four existing NCI-60 microRNA datasets, the concordance of the new expression dataset with the other four was modest, with mean Pearson correlation coefficients of 0.37-0.54. In spite of this, comparable results with different datasets were noted in clustering of the cell-lines by their microRNA expression, differential expression of microRNAs by the lines' tissue of origin, and correlation of specific microRNAs with the doubling-time of cells or their radiation sensitivity. Mutation status of the cell-lines for the TP53, PTEN and BRAF but not CDKN2A or KRAS cancer-related genes was found to be associated with changes in expression of specific microRNAs. The microRNA dataset generated here should be valuable to those working in the field of microRNAs as well as in integromic studies of the NCI-60 panel.

| S-EPMC3509128 | biostudies-literature

Quantitative Proteome Landscape of the NCI-60 Cancer Cell Lines.

Project description:Here we describe a proteomic data resource for the NCI-60 cell lines generated by pressure cycling technology and SWATH mass spectrometry. We developed the DIA-expert software to curate and visualize the SWATH data, leading to reproducible detection of over 3,100 SwissProt proteotypic proteins and systematic quantification of pathway activities. Stoichiometric relationships of interacting proteins for DNA replication, repair, the chromatin remodeling NuRD complex, β-catenin, RNA metabolism, and prefoldins are more evident than that at the mRNA level. The data are available in CellMiner (discover.nci.nih.gov/cellminercdb and discover.nci.nih.gov/cellminer), allowing casual users to test hypotheses and perform integrative, cross-database analyses of multi-omic drug response correlations for over 20,000 drugs. We demonstrate the value of proteome data in predicting drug response for over 240 clinically relevant chemotherapeutic and targeted therapies. In summary, we present a novel proteome resource for the NCI-60, together with relevant software tools, and demonstrate the benefit of proteome analyses.

| S-EPMC6889472 | biostudies-literature

Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy

Project description:Background Immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized cancer therapy. However, therapeutic targeting of inhibitory T cell receptors such as PD-1 not only initiates a broad immune response against tumors, but also causes severe adverse effects. An ideal future stratified immunotherapy would interfere with cancer-specific cell surface receptors only. Methods To identify such candidates, we profiled the surface receptors of the NCI-60 tumor cell panel via flow cytometry. The resulting surface receptor expression data were integrated into proteomic and transcriptomic NCI-60 datasets applying a sophisticated multiomics multiple co-inertia analysis (MCIA). This allowed us to identify surface profiles for skin, brain, colon, kidney, and bone marrow derived cell lines and cancer entity-specific cell surface receptor biomarkers for colon and renal cancer. Results For colon cancer, identified biomarkers are CD15, CD104, CD324, CD326, CD49f, and for renal cancer, CD24, CD26, CD106 (VCAM1), EGFR, SSEA-3 (B3GALT5), SSEA-4 (TMCC1), TIM1 (HAVCR1), and TRA-1-60R (PODXL). Further data mining revealed that CD106 (VCAM1) in particular is a promising novel immunotherapeutic target for the treatment of renal cancer. Conclusion Altogether, our innovative multiomics analysis of the NCI-60 panel represents a highly valuable resource for uncovering surface receptors that could be further exploited for diagnostic and therapeutic purposes in the context of cancer immunotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-022-02710-y.

| S-EPMC9555072 | biostudies-literature

Proteomic profiling of the NCI-60 cancer cell lines using new high-density reverse-phase lysate microarrays.

Project description:Because most potential molecular markers and targets are proteins, proteomic profiling is expected to yield more direct answers to functional and pharmacological questions than does transcriptional profiling. To aid in such studies, we have developed a protocol for making reverse-phase protein lysate microarrays with larger numbers of spots than previously feasible. Our first application of these arrays was to profiling of the 60 human cancer cell lines (NCI-60) used by the National Cancer Institute to screen compounds for anticancer activity. Each glass slide microarray included 648 lysate spots representing the NCI-60 cell lines plus controls, each at 10 two-fold serial dilutions to provide a wide dynamic range. Mouse monoclonal antibodies and the catalyzed signal amplification system were used for immunoquantitation. The signal levels from the >30,000 data points for our first 52 antibodies were analyzed by using p-scan and a quantitative dose interpolation method. Clustered image maps revealed biologically interpretable patterns of protein expression. Among the principal early findings from these arrays were two promising pathological markers for distinguishing colon from ovarian adenocarcinomas. When we compared the patterns of protein expression with those we had obtained for the same genes at the mRNA level by using both cDNA and oligonucleotide arrays, a striking regularity appeared: cell-structure-related proteins almost invariably showed a high correlation between mRNA and protein levels across the NCI-60 cell lines, whereas non-cell-structure-related proteins showed poor correlation.

| S-EPMC283574 | biostudies-literature

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