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GSE21147
Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The retinoblastoma (Rb) tumor suppressor is often inactivated in cancers. To identify genes that can be used to specifically target such cancers, we carried out a genetic screen in Drosophila. We identified gig (fly TSC2) and found that inactivation of rbf (fly Rb) and gig synergistically induced cell death. Interestingly, inactivation of TSC2 specifically kills Rb mutant cancer cells under stress conditions, which is correlated with an inhibition of tumor growth. We show that cancer cell killing induced by concomitant inactivation of Rb and TSC2 is mediated by increased cellular stress, including oxidative stress. Inactivation of TSC2 and Rb synergistically induce oxidative stress via increased protein synthesis, inhibited de novo lipid synthesis, and decreased ROS scavenger enzyme SOD2 induction.
Publication Title
Specific killing of Rb mutant cancer cells by inactivating TSC2.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 32 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
There is a critical need in cancer therapeutics to identify targeted therapies that will improve outcomes and decrease toxicities compared to conventional, cytotoxic chemotherapy. Ewing sarcoma is a highly aggressive bone and soft tissue cancer that is caused by the EWS-FLI1 fusion protein. Although EWS-FLI1 is specific for cancer cells, and required for tumorigenesis, directly targeting this transcription factor has proven challenging. Consequently, targeting unique dependencies or key downstream mediators of EWS-FLI1 represent important alternative strategies. We used gene expression data derived from a genetically defined model of Ewing sarcoma to interrogate the Connectivity Map and identify a class of drugs, iron chelators, that downregulate a significant number of EWS-FLI1 target genes. We then identified ribonucleotide reductase M2 (RRM2), the iron-dependent subunit of ribonucleotide reductase (RNR), as one mediator of iron chelator toxicity in Ewing sarcoma cells. Inhibition of RNR in Ewing sarcoma cells led to apoptosis and cell death in vitro and attenuated tumor growth in vivo in a xenograft model. Additionally, we discovered that the sensitivity of Ewing sarcoma cells to inhibition or suppression of RNR is mediated, in part, by high levels of SLFN11, a protein that sensitizes cells to DNA damage. This work demonstrates a unique dependency of Ewing sarcoma cells on RNR and supports further exploration of clinically used inhibitors of RNR as a therapeutic approach in treating this cancer.
Publication Title
Gene expression signature based screening identifies ribonucleotide reductase as a candidate therapeutic target in Ewing sarcoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Oncogenic transformation in Ewing sarcoma tumors is driven by the fusion oncogene EWS-FLI1. The inducible expression of EWS-FLI1 (EF) in embryoid bodies, or collections of differentiating stem cells, generates cells with properties of Ewing sarcoma tumors, including characteristics of transformation. These cell lines exhibit anchorage-independent growth, a lack of contact inhibition and a strong Ewing sarcoma gene expression signature. These cells also demonstrate a requirement for the persistent expression of EWS-FLI1 for cell survival and growth.
Publication Title
Modeling the initiation of Ewing sarcoma tumorigenesis in differentiating human embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Host responses to intracellular UPEC communities
Publication Title
Functional genomic studies of uropathogenic Escherichia coli and host urothelial cells when intracellular bacterial communities are assembled.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
Illumina HiSeq 2000
Description
By transcriptome (RNA-Seq) analysis of PC-3 or DU145 prostate cancer cell lines over- or under-expressing NUSAP1, we determined genes that become differentially expressed upon expression changes of NUSAP1. Ingenuity Pathway Analysis revealed that the differentially expressed genes correlated with increased tumor progression and are involved in functions that include cancer, cellular movement, and cell morphology Overall design: Lentiviral infections were used to over- or under-express NUSAP1 or controls in triplicate in PC-3 or DU145 cell lines. Seventy-two or ninety-six hours after infection, total RNA was extracted and purified. The sequencing libraries were prepared with the TruSeq RNA Sample Preparation Kit v2 (Illumina) or TruSeq Stranded mRNA Sample Preparation Kit (Illumina) as directed by the manufacturer’s protocol. Pooled libraries were run on a Hiseq 2000 Sequencing System (Illumina) with 101 base pair single-end reads.
Publication Title
NUSAP1 promotes invasion and metastasis of prostate cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Monocytes were induced to mature to macrophages with M-CSF. Cells were then activated with Interferon gamma and LPS or IL-4.
Publication Title
Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We compared gene expression in the small intestine (ileum) of mice that were either (i) germ-free, (ii) colonized with a conventional mouse cecal microbiota, (iii) colonized with a conventional zebrafish gut microbiota, or (iv) colonized with Pseudomonas aeruginosa PAO1.
Publication Title
Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Wildtype B6, Rag1-/- B6 and Rag1-/- B6 mice harboring the 225.4 IgA producing hybridoma were colonized for 10 days with Bacteroides thetaiotaomicron
Publication Title
IgA response to symbiotic bacteria as a mediator of gut homeostasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Telogen is not simply a quiescent part of the hair cycle
Publication Title
Identification of telogen markers underscores that telogen is far from a quiescent hair cycle phase.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 53 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To characterize genes, pathways, and transcriptional regulators enriched in the mouse cornea, we compared the expression profiles of whole mouse cornea, bladder, esophagus, lung, proximal small intestine, skin, stomach, and trachea.
Publication Title
The Ets transcription factor EHF as a regulator of cornea epithelial cell identity.
Sample Metadata Fields
Specimen part
View Samples