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accession-icon GSE20540
Gene expression profiles of myeloma cells interacting with bone marrow stromal cells in vitro
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Conventional anti-cancer drug screening is typically performed in the absence of accessory cells (e.g. stromal cells) of the tumor microenvironment, which can profoundly alter anti-tumor drug activity. To address this major limitation, we have developed assays (e.g. the tumor cell-specific in vitro bioluminescence imaging (CS-BLI) assay) to selectively quantify tumor cell viability, in presence vs. absence of non-malignant stromal cells or drug treatment. These assays have allowed us to identify that neoplastic cells from diverse malignancies exhibit stroma-induced resistance to different anti-tumor agents. In this analysis, we evaluated the molecular changes triggered in myeloma cells by their in vitro interaction with stromal cells. The transcriptional profile of 3 human multiple myeloma (MM) cell lines (MM.1S, MM.1R, INA-6) co-cultured with stromal cells vs. when cultured alone was characterized by oligonucleotide microarray analysis, using the human U133 plus 2.0 Affymetrix GeneChip.

Publication Title

Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity.

Sample Metadata Fields

Cell line

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accession-icon GSE49124
Expression data from JQ1 (0.2 uM) treated tamoxifen-resistant MCF7 cells
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Estrogen signaling pathway is critical for breast cancer development and has remained the major adjuvant therapeutic target for this disease. Tamoxifen has been used in clinic for many years to treat ER-positive breast cancer. However a great many (30%) suffer relapse due to drug resistance. In this study, the bromodomain inhibitor JQ1 was found to down-regulate ERalpha gene expression and have anti-tumor effect in cultured tamoxifen-resisant breast cancer cells.

Publication Title

An epigenomic approach to therapy for tamoxifen-resistant breast cancer.

Sample Metadata Fields

Cell line, Treatment

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accession-icon SRP021517
Gene Expression Analysis of Zebrafish Melanocytes, Iridophores, and Retinal Pigmented Epithelium Reveals Indicators of Biological Function and Developmental Origin
  • organism-icon Danio rerio
  • sample-icon 35 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000, IlluminaGenomeAnalyzerIIx

Description

In order to facilitate understanding of pigment cell biology, we developed a method to concomitantly purify melanocytes, iridophores, and retinal pigmented epithelium from zebrafish, and analyzed their transcriptomes. Comparing expression data from these cell types and whole embryos allowed us to reveal gene expression co-enrichment in melanocytes and retinal pigmented epithelium, as well as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes and retinal pigmented epithelium, indicating the shared functions of melanin-producing cells. We found 62 genes significantly co-enriched in melanocytes and iridophores, illustrative of their shared developmental origins from the neural crest. This is also the first analysis of the iridophore transcriptome. Gene expression analysis for iridophores revealed extensive enrichment of specific enzymes to coordinate production of their guanine-based reflective pigment. We speculate the coordinated upregulation of specific enzymes from several metabolic pathways recycles the rate-limiting substrate for purine synthesis, phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification procedure and expression analysis described here, along with the accompanying transcriptome-wide expression data, provide the first mRNA sequencing data for multiple purified zebrafish pigment cell types, and will be a useful resource for further studies of pigment cell biology. Overall design: mRNA profiles of zebrafish pigment cells were generated using Illumina GAIIX sequencing

Publication Title

Gene expression analysis of zebrafish melanocytes, iridophores, and retinal pigmented epithelium reveals indicators of biological function and developmental origin.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE63539
GATA2 facilitates steroid receptor coactivator (SRC) recruitment to the androgen receptor (AR) complex
  • organism-icon Homo sapiens
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon (ffymetrixhumanexon1.0starray[cdf:huex10stv2,corer3,a20071112,ep)

Description

The androgen receptor (AR) is a key driver of prostate cancer (PC), even in the state of castration-resistant PC (CRPC), and frequently even after treatment with second-line hormonal therapies such as abiraterone and enzalutamide. The persistence of AR activity via both ligand-dependent and ligand-independent (including constitutively active AR splice variants) mechanisms highlights the unmet need for alternative approaches to block AR signaling in CRPC. We investigated the transcription factor GATA2 as a regulator of AR signaling and a novel therapeutic target in PC. We demonstrate that GATA2 directly promotes AR expression (both full-length and splice variant), resulting in a strong positive correlation between GATA2 and AR expression in PC (cell lines and patient specimens). Conversely, GATA2 expression is repressed by androgen and AR, suggesting a negative feedback regulatory loop that, upon androgen deprivation, derepresses GATA2 to contribute to AR overexpression in CRPC. Simultaneously, GATA2 is necessary for optimal transcriptional activity of AR (both full-length and splice variant). GATA2 co-localizes with AR and FOXA1 on chromatin to enhance recruitment of steroid receptor coactivators (SRCs) and formation of the transcriptional holocomplex. In agreement with these important functions, high GATA2 expression and transcriptional activity predicted for worse clinical outcome in PC patients. A GATA2 small molecule inhibitor suppressed the expression and transcriptional function of AR (both full-length and splice variant) and exerted potent anticancer activity against PC cell lines. We propose pharmacological inhibition of GATA2 as a first-in-field approach to target AR expression and function and improve outcomes in CRPC.

Publication Title

GATA2 facilitates steroid receptor coactivator recruitment to the androgen receptor complex.

Sample Metadata Fields

Cell line

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accession-icon GSE56149
Microarray analysis of a Drosophila dopamine transporter mutant, fumin (fmn)
  • organism-icon Drosophila melanogaster
  • sample-icon 13 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome 2.0 Array (drosophila2)

Description

We previously found a short sleeper mutant, fmn, and identified its mutation in the dopamine transporter gene. In an attempt to discover additional sleep related genes in Drosophila, we carried out a microarray analysis comparing mRNA expression in heads of fmn and control flies and found differentially expressed genes.

Publication Title

The NMDA Receptor Promotes Sleep in the Fruit Fly, Drosophila melanogaster.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP132263
RNA-seq analysis of BAP1-depleted uveal melanoma cells
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

OCM-1A uveal melanoma cells were infected with lentivirus carrying shRNA expression constructs specific for BAP1 or GFP (control), and placed under selection for 6 days. RNA-seq was performed. Overall design: Samples represent three independent experiments treated with control or BAP1 shRNA

Publication Title

Transposase mapping identifies the genomic targets of BAP1 in uveal melanoma.

Sample Metadata Fields

Specimen part, Cell line, Treatment, Subject, Time

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accession-icon GSE81440
Identification of an NKX3.1-G9a-UTY regulatory network that controls prostate differentiation
  • organism-icon Mus musculus, Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)

Description

To investigate the role of NKX3.1 in prostate differentiation, we employed transcriptome analysis of mouse seminal vesicle (from 15-month-old Nkx3.1+/+ mice); mouse prostate (from 4-month-old Nkx3.1+/+ and Nkx3.1-/- mice); human prostate cells (RWPE1 cells engineered with empty vector (altered pTRIPZ), NKX3.1 wild type over-expression, and NKX3.1 (T164A) mutant over-expression); and tissue recombinants (generated from combining engineered mouse epithelial cells (seminal vesicle epithelial cells or prostate epithelial cells from 2-month-old mice) and rat UGS mesenchymal cells). Mouse tissue or human cells were snap frozen for subsequent molecular analysis.

Publication Title

Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation.

Sample Metadata Fields

Age, Specimen part, Cell line

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accession-icon GSE69214
Predicting drug response in human prostate cancer from preclinical analysis of in vivo mouse models
  • organism-icon Mus musculus
  • sample-icon 35 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 expression beadchip

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Predicting Drug Response in Human Prostate Cancer from Preclinical Analysis of In Vivo Mouse Models.

Sample Metadata Fields

Specimen part, Disease, Disease stage, Treatment

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accession-icon GSE69211
Predicting drug response in human prostate cancer from preclinical analysis of in vivo mouse models (I)
  • organism-icon Mus musculus
  • sample-icon 28 Downloadable Samples
  • Technology Badge IconIllumina MouseWG-6 v2.0 expression beadchip

Description

Analysis of the transcriptome of mouse models of prostate cancer after treatment with rapamycin and PD0325901 combination therapy or standard of care docetaxel. The Nkx3.1CreERT2/+; Ptenflox/flox; KrasLSL-G12D/+ (NPK mice) was used in this study. Two months after tumor induction, mice were randomly assigned to vehicle (Veh) or treatments groups, such as rapamycin and PD0325901 (RAPPD) or docetaxel (Docetaxel). For the treatment groups mice were administered rapamycin (10 mg/kg) and PD0325901 (10 mg/kg) or docetaxel (10 mg/kg) for 5 days (SHORT) or for 1 month (LONG). At the end of the treatment, mice were euthanized, tumors harvested and snap frozen for subsequent molecular analysis.

Publication Title

Predicting Drug Response in Human Prostate Cancer from Preclinical Analysis of In Vivo Mouse Models.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE24169
Finding direct target genes of VND7
  • organism-icon Arabidopsis thaliana
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

The Arabidopsis thaliana NAC domain transcription factor, VASCULAR-RELATED NAC-DOMAIN7 (VND7), acts as a key regulator of xylem vessel differentiation. In order to identify direct target genes of VND7, we performed global transcriptome analysis using Arabidopsis transgenic lines in which VND7 activity could be induced post-translationally. This analysis identified 63 putative direct target genes of VND7, which encode a broad range of proteins, such as transcription factors, IRREGULAR XYLEM proteins and proteolytic enzymes, known to be closely associated with xylem vessel formation. Recombinant VND7 protein binds to several promoter sequences present in candidate direct target genes: specifically, in the promoter of XYLEM CYSTEINE PEPTIDASE1, two distinct regions were demonstrated to be responsible for VND7 binding. We also found that expression of VND7 restores secondary cell wall formation in the fiber cells of inflorescence stems of nst1nst3 double mutants, as well as expression of NAC SECONDARY WALL THICKENING PROMOTING FACTOR3 (NST3, however, the vessel-type secondary wall deposition was observed only as a result of VND7 expression. These findings indicated that VND7 upregulates, directly and/or indirectly, many genes involved in a wide range of processes in xylem vessel differentiation, and that its target genes are partially different from those of NSTs.

Publication Title

VASCULAR-RELATED NAC-DOMAIN7 directly regulates the expression of a broad range of genes for xylem vessel formation.

Sample Metadata Fields

Age, Specimen part, Treatment

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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