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Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in proliferation, motility, adhesion, invasion, angiogenesis, and survival signaling. Focal adhesion kinase has been shown to be overexpressed in many types of tumors, including breast cancer at early stages of tumorigenesis. To study the biological role of FAK in breast tumorigenesis, we used FAKsiRNA to down-regulate FAK in MCF-7 cell lines.
Publication Title
The direct effect of focal adhesion kinase (FAK), dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Expression of the MT1-MMP gene induces a significant upregulation of of oncogenes and tumorignenic genes in 184B5-MT1 cells.
Publication Title
Membrane type-1 matrix metalloproteinase confers aneuploidy and tumorigenicity on mammary epithelial cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human pluripotent stem cells (hPSC) generate hematopoietic progenitor cells (HPC), but fail to engraft xenograft models, which is a hallmark feature of adult/somatic hematopoietic stem cells (HSC) from human donors. Progress to derive hPSC-derived HSCs has relied on cell autonomous approaches that force expression of transcription factors (TF), however the role of bone marrow (BM) niche remains poorly understood. Here, we quantified a failure of hPSC-HPCs to survive even in the first 24 h upon transplantation into the BM. Across several hPSC-HPC differentiation methodologies, we identified the lack of CXCR4 expression and network function. Ectopic CXCR4 conferred CXCL12-dependent signaling of hPSC-HPCs in biochemical assays and increased migration/chemotaxis and progenitor capacity, as well as survival and proliferation following transplantation in vivo. In addition, hPSC-HPCs forced to express CXCR4 demonstrated a transcriptional shift toward somatic HPCs, but this approach failed to produce long-term HSC engraftment. Our results reveal that independent of differentiation methods, networks involving CXCR4 should be targeted to generate HSCs with in vivo function from hPSCs.
Publication Title
CXCL12/CXCR4 Signaling Enhances Human PSC-Derived Hematopoietic Progenitor Function and Overcomes Early In Vivo Transplantation Failure.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We conducted a proof-of-concept experiment to explore the possibility of using gene expression-based high throughput screening (GE-HTS) to find inhibitors of a signaling cascade, using platelet derived growth factor receptor (PDGFR) signaling as the example.
Publication Title
Gene expression-based screening for inhibitors of PDGFR signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation.
Publication Title
Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 50 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we prioritized 15 candidate compounds (2 were already confirmed in the literature). We next evaluated the 13 remaining compounds. Eight reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation.
Publication Title
Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Cure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted.
Publication Title
Gefitinib induces myeloid differentiation of acute myeloid leukemia.
Sample Metadata Fields
Disease, Disease stage, Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Inherited genetic risk factors play an important role in cancer. However, other than cancer susceptibility genes found in familial cancer syndromes and inherited in a Mendelian fashion, little is known about modifier genes (germline variants that interact with each other and with environmental factors) that contribute to individual susceptibility. Here we develop a strategy parental strain expression mapping (PSEM), which utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses, to directly identify candidate germline modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. In keeping with findings in murine models, the expression of the glycolysis pathway was strongly enriched in the non-cancer prostate tissue from patients with prostate cancer who did not recur after surgical resection. Together these data suggest that PSEM can directly identify germline modifier pathways of relevance to human disease.
Publication Title
Identification of prostate cancer modifier pathways using parental strain expression mapping.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133A Array (hgu133a)
Description
We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. We tested several of these in duplicate replicates in blasts from a patient with APL. Also included in this data set are a collection of 6 primary patient AML cells, 3 normal neutrophils samples, and 3 normal monocyte samples. This data was used to evaluate whole genome effects of the compounds on APL cells in relation to AML versus normal neutrophils and monocytes.
Publication Title
Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE5007- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This study compared the expression signatures of HL60 cells +/- tretinoin. This data was then used for another study showing a method for high-throughput gene expression signature analysis.
Publication Title
A method for high-throughput gene expression signature analysis.
Sample Metadata Fields
No sample metadata fields
View Samples