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GSE24592
Homo sapiens
30 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The nuclear hormone receptor, estrogen receptor-alpha (ER), and MAP kinases both play key roles in hormone-dependent cancers, yet their interplay and the integration of their signaling inputs remain poorly understood. In these studies, we document that estrogen-occupied ER activates and interacts with ERK2, a downstream effector in the MAPK pathway, resulting in ERK2 and ER colocalization at chromatin binding sites across the genome of breast cancer cells.
Publication Title
Genomic collaboration of estrogen receptor alpha and extracellular signal-regulated kinase 2 in regulating gene and proliferation programs.
Sample Metadata Fields
Disease, Disease stage, Cell line, Time
View Samples- Homo sapiens
- 17 Downloadable Samples
NextSeq 500
Description
Based on RNA-seq, we performed transcriptomic profiling to examine the similarities or differences between BICA (bone-in-culture array) and IVBL (in vivo bone lesion). CIBERSORT analysis reveals that the major local cellular components are comparable between BICA and IVBL, but differ dramatically in orthotopic tumors. Principle component analysis of human RNAs indicated that the transcriptomic profiles of cancer cells in BICA are more closely mimicking IVBL, as compared to cancer cells in 2D and in orthotopic tumors. These results provide transcriptome-wide evidence supporting BICA as a platform to mimic bone microenvironment. Overall design: 2D culture cells, orthotopic tumors, BICA samples and bone lesions, all developed by MCF-7, are subject to NGS and then analyzed.
Publication Title
Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- NextSeq 500
Description
To investigate the impact of CD4+ T cells on tumor vasculature, we performed transcriptome profiling on tumor-associated endothelial cells in mice with or without functional CD4 T cells. In addition to examining four pathways that affect vessel maturation (VEGFA, ANGPT1/ANGPT2, TGFbR, and sphingolipid metabolism), we ran Gene Set Enrichment Analysis (GSEA) and found a down-regulation of cellular adhesion and extracellular matrix assembly-related pathways in the CD4 T cell deficient group. This suggests that CD4+ T cells play an important role in promoting tumor vessel integrity and normalization. Overall design: Transcriptome profiling of E0771 murine tumor-associated endothelial cells isolated from CD4+ T cell competent (CD8KO, Tie2Cre, WT) or deficient mouse strains (CD4KO, Tie2Cre;H2Ab flox and TCRKO) .
Publication Title
Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing strategy, we mapped estrogen receptor alpha (ERalpha) binding sites in MCF-7 breast cancer cells. We identified 1,234 high confidence binding clusters of which 94% are projected to be bona fide ERalpha binding regions. Only 5% of the mapped estrogen receptor binding sites are located within 5 kb upstream of the transcriptional start sites of adjacent genes, regions containing the proximal promoters, whereas vast majority of the sites are mapped to intronic or distal locations (>5 kb from 5' and 3' ends of adjacent transcript), suggesting transcriptional regulatory mechanisms over significant physical distances. Of all the identified sites, 71% harbored putative full estrogen response elements (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences. Genes in the vicinity of ERalpha binding sites were enriched for regulation by estradiol in MCF-7 cells, and their expression profiles in patient samples segregate ERalpha-positive from ERalpha-negative breast tumors. The expression dynamics of the genes adjacent to ERalpha binding sites suggest a direct induction of gene expression through binding to ERE-like sequences, whereas transcriptional repression by ERalpha appears to be through indirect mechanisms. Our analysis also indicates a number of candidate transcription factor binding sites adjacent to occupied EREs at frequencies much greater than by chance, including the previously reported FOXA1 sites, and demonstrate the potential involvement of one such putative adjacent factor, Sp1, in the global regulation of ERalpha target genes. Unexpectedly, we found that only 22%-24% of the bona fide human ERalpha binding sites were overlapping conserved regions in whole genome vertebrate alignments, which suggest limited conservation of functional binding sites. Taken together, this genome-scale analysis suggests complex but definable rules governing ERalpha binding and gene regulation.
Publication Title
Whole-genome cartography of estrogen receptor alpha binding sites.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
ARC (NSC 188491, SMA-491), 4-amino-6-hydrazino-7-beta-d-ribofuranosyl-7H-pyrrolo-(2,3-d)-pyrimidine-5-carboxamide, is a nucleoside analog with profound in vitro anti-cancer activity. First identified in a high-throughput screen for inhibitors of p21 mRNA expression, subsequent experiments showed that ARC also repressed expression of hdm2 and survivin, leading to its classification as a global inhibitor of transcription 1. The following Hu U133 plus 2.0 arrays represent single time point (24 hour) gene expression analysis of transcripts altered by ARC treatment. Arrays for the other compounds (sangivamycin and doxorubicin) are included as comparators.
Publication Title
ARC (NSC 188491) has identical activity to Sangivamycin (NSC 65346) including inhibition of both P-TEFb and PKC.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic non-healing venous leg ulcers (VLUs) are a widespread debilitating disease with high morbidity and associated costs, as approximately $15 billion annually are spent on the care of VLUs. Despite their socioeconomic burden, there is a paucity of novel treatments targeted towards healing VLUs, which can be attributed to both lack of pathophysiologic insight into VLU development as well as lack of knowledge regarding biologic actions of VLU-targeted therapies. Currently, the bioengineered bilayered living cellular construct (BLCC) skin substitute is the only FDA-approved biologic treatment for healing VLUs. To elucidate the mechanisms through which the BLCC promotes healing of chronic VLUs, we conducted a clinical trial (NCT01327937) in which patients with non-healing VLUs were treated with either standard care (compression therapy) or with BLCC together with standard care. Tissue was collected from the VLU edge before and 1 week after treatment, and samples underwent comprehensive microarray, mRNA and protein analyses. Ulcers treated with BLCC skin substitute displayed three distinct patterns suggesting the mechanisms by which BLCC shifted a non-healing into a healing tissue response: it modulated inflammatory and growth factor signaling; it activated keratinocytes; and it attenuated Wnt/-catenin signaling. In these ways, BLCC application orchestrated a shift of the chronic non-healing ulcer microenvironment into a distinctive healing milieu resembling that of an acute, healing wound. Our findings also provide first patient-derived in vivo evidence of specific biologic processes that can be targeted in the design of therapies to promote healing of chronic VLUs.
Publication Title
A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers.
Sample Metadata Fields
Specimen part, Disease stage, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Diabetic foot ulcers (DFUs) are the leading cause of lower leg amputations in diabetic population. To better understand molecular pathophysiology of DFUs we used patients specimens and genomic profiling. We identified 3900 genes specifically regulated in DFUs. Moreover, we compared DFU to human skin acute wound (AW) profiles and found DNA repair mechanisms and regulation of gene expression among the processes specifically suppressed in DFUs, whereas essential wound healing-related processes, inflammatory/immune response or cell migration, were not activated properly. To identify potential regulators of DFU-specific genes, we used upstream target analysis. We found miR-15/16 family enriched in DFUs, but not in AW, which was confirmed by qPCR. We found that infection with the most common DFU colonizer, Staphylococcus aureus, triggers induction of miR-15-5p, which in turn, targets multiple DFU-specific genes, including genes involved in DNA repair (WEE1, MSH2 and RAD50) and the regulator of inflammatory pathway, IKBKB. Induction of miR-15b-5p, either by miR-mimic transfection in vitro or by S. aureus infection of acute wounds ex vivo, suppressed both WEE1 and IKBKB. Consequently, we detected an increase in DNA double strand breaks in DFUs. In summary, our data indicate that S. aureus infection, via induction of miR-15b-5p, may lead to suppression of DNA repair mechanisms and a sub-optimal inflammatory response, contributing to pathophysiology of DFU patients
Publication Title
Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Primary human hepatocytes (PHHs) are a liver-specific cell subtype, and we have shown that these cells respond in a unique manner to the introduction of hepatitis C viral RNA (HCV vRNA) derived from different genotypes of the virus.
Publication Title
Transmitted/founder hepatitis C viruses induce cell-type- and genotype-specific differences in innate signaling within the liver.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 818 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Xenograft models remain a cornerstone technology in the development of anti-cancer agents. The ability of immunocompromised rodents to support the growth of human tumors provides an invaluable transition between in vitro testing and clinical trials. Therefore, approaches to improve model selection are required. In this study, cDNA microarray data was generated for a collection of xenograft models at in vivo passages 1, 4 and 10 (P1, P4 and P10) along with originating cell lines (P0). These data can be mined to determine transcript expression 1) relative to other models 2) with successive in vivo passage and 3) during the in vitro (P0) to in vivo (P1) transition.
Publication Title
Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages--strategies for data mining in support of therapeutic studies.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptomic studies of human tumor xenografts are complicated by the presence of murine cellular mRNA. As such, it is useful to know the extent to which mouse mRNA cross-hybridizes to any given array platform. In this study, murine cDNA samples from diverse sources were hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays. In this regard it is possible to identify specific probes that are potential targets of cross-species interference.
Publication Title
Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages--strategies for data mining in support of therapeutic studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples