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GSE52707
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Breast cancers with HER2 overexpression are sensitive to drugs targeting the receptor or its kinase activity. HER2-targeting drugs are initially effective against HER2- positive breast cancer, but resistance inevitably occurs. We previously found that nuclear factor kappa B is hyper-activated in the subset of HER-2 positive breast cancer cells and tissue specimens. In this study, we report that constitutively active NF-B rendered HER2-positive cancer cells resistant to anti-HER2 drugs, and cells selected for Lapatinib resistance up-regulated NF-B. In both circumstances, cells were anti-apoptotic and grew rapidly as xenografts. Lapatinib-resistant cells were refractory to HER2 and NF-B inhibitors alone but were sensitive to their combination, suggesting a novel therapeutic strategy. A subset of NF-B-responsive genes was overexpressed in HER2-positive and triple-negative breast cancers, and patients with this NF-B signature had poor clinical outcome. Anti-HER2 drug resistance may be a consequence of NF-B activation, and selection for resistance results in NF-B activation, suggesting this transcription factor is central to oncogenesis and drug resistance. Clinically, the combined targeting of HER2 and NF-B suggests a potential treatment paradigm for patients who relapse after anti-HER2 therapy. Patients with these cancers may be treated by simultaneously suppressing HER2 signaling and NF-B activation.
Publication Title
NF-κB activation-induced anti-apoptosis renders HER2-positive cells drug resistant and accelerates tumor growth.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene transfer into HSCs by gammaretroviral vectors (RV) is an effective treatment for inherited blood disorders, although potentially limited by the risk of insertional mutagenesis. We evaluated the genomic impact of RV integration in T-lymphocytes from adenosine deaminase (ADA)-Severe combined immunodeficiency (SCID) patients 10 to 30 months after infusion of autologous, genetically-corrected CD34+ cells. Expression profiling on ex vivo T-cell bulk population revealed no difference with respect to healthy controls. To assess the effect of vector integration on gene expression at the single cell level, primary T-cell clones were isolated from two patients. T-cell clones harboured either one or two vector copies per cell and displayed partial to full correction of ADA expression, purine metabolism and TCR-driven functions. Analysis of retroviral integration sites (RIS) indicated a high diversity in T-cell origin, consistent with the polyclonal TCR-Vbeta repertoire. Quantitative transcript analysis of 120 genes within a 200kb-window around RIS showed modest (2.8- to 5.2-fold) disregulation of 5.8% genes in 18.6% of the T-cell clones compared to controls. Nonetheless, affected clones maintained a stable phenotype and normal functions in vitro. These results confirm that RV-mediated gene transfer for ADA-SCID is safe, and provide crucial information for the development of future gene therapy protocols.
Publication Title
Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 26 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This work uses a time series in order to decipher gene relationships and consequently to build core regulatory networks involved in Arabidopsis root adaptation to NO3- provision. The experimental approach has been to monitor genome response to NO3- at 3, 6, 9, 12, 15 and 20 min, using ATH1 chips. This high-resolution time course analysis demonstrated that the previously known primary nitrate response is actually preceded by very fast (within 3 min) gene expression modulation, involving genes/functions needed to prepare plants to use/reduce NO3-. State-space modeling (a machine learning approach) has been used to successfully predict gene behavior in unlearnt conditions.
Publication Title
Predictive network modeling of the high-resolution dynamic plant transcriptome in response to nitrate.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
Comparatative gene expression analysis for CD4 T cell subsets isolated from peripheral blood and palatine tonsils
Publication Title
A methodology for global validation of microarray experiments.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
DNA microarrays are popular tools for measuring gene expression of biological samples. This ever increasing popularity is ensuring that a large number of microarray studies are conducted, many of which with data publicly available for mining by other investigators. Under most circumstances, validation of differential expression of genes is performed on a gene to gene basis. Thus, it is not possible to generalize validation results to the remaining majority of non-validated genes or to evaluate the overall quality of these studies. <br></br> We have devised an approach for the global validation of DNA microarray experiments that will allow researchers to evaluate the general quality of their experiment and to extrapolate validation results of a subset of genes to the remaining non-validated genes. We applied this method to a microarray experiment validated with quantitative real time polymerase chain reaction. The experiment consists of three biological replicate treatments of mouse 3T3-L1 preadipocytes with the steroid hormone dexamethasone for 3 hours. Total RNA was extracted from each of our three treatment and three control samples, and we labeled and hybridized five aliquots of each sample to Affymetrix MGU74Av2 microarrays, for a total of 30 microarrays.<br></br> We illustrate why the popular strategy of selecting only the most differentially expressed genes for validation generally fails as a global validation strategy and propose random-stratified sampling as a better gene selection method. We also illustrate shortcomings of often-used validation indices such as overlap of significant effects and the correlation coefficient and recommend the concordance correlation coefficient (CCC) as an alternative.
Publication Title
A methodology for global validation of microarray experiments.
Sample Metadata Fields
Cell line, Subject, Compound
View Samples- Homo sapiens
- 81 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Interferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS). However, no information regarding blood transcriptional changes induced by IFN treatment in SPMS patients is available.
Publication Title
Transcriptional response to interferon beta-1a treatment in patients with secondary progressive multiple sclerosis.
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The glycopeptide antibiotic vancomycin (VCM) represents one of the last lines of defense against methicillin-resistant Staphylococcus aureus infections. However, vancomycin is nephrotoxic, but the mechanism of toxicity is still unclear.
Publication Title
Gene expression analysis reveals new possible mechanisms of vancomycin-induced nephrotoxicity and identifies gene markers candidates.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The regeneration of diseased hyaline cartilage remains a great challenge, mainly because degeneration activities after major injury or due to age-related processes overwhelm the self-renewal capacity of the tissue. We show that repair tissue from human articular cartilage of late stages of osteoarthritis harbor a unique progenitor cell population, termed chondrogenic progenitor cells exhibiting stem cell characteristics, such as multipotency, lack of immune system activation and, in particular, migratory activity. The isolated CPC exhibit a high chondrogenic potential and were able to populate diseased tissue in vivo. Moreover, down-regulation of the osteogenic transcription factor runx-2 enhanced the expression of the chondrogenic transcription factor sox-9 and consequently the matrix synthesis potential of chondrogenic progenitor cells. Our results, while offering new insight into the biology of progenitor cells from diseased cartilage tissue, might assist future strategies to treat late stages of osteoarthritis.
Publication Title
Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
IlluminaHiSeq2000
Description
Analysis of Allelic bias in clonal lymphoblastoid cells. Abstract: In mammals, numerous autosomal genes are subject to mitotically stable monoallelic expression (MAE), including genes that play critical roles in a variety of human diseases. Due to challenges posed by the clonal nature of MAE, very little is known about its regulation; in particular, no molecular features have been specifically linked to MAE. Here we report an approach that distinguishes MAE genes in human cells with great accuracy: a chromatin signature consisting of chromatin marks associated with active transcription (H3K36me3) and silencing (H3K27me3) simultaneously occurring in the gene body. The MAE signature is present in ~20% of ubiquitously expressed genes and over 30% of tissue-specific genes across cell types. Notably, it is enriched among key developmental genes that have bivalent chromatin structure in pluripotent cells. Our results open a new approach to the study of MAE that is independent of polymorphisms, and suggest that MAE is linked to cell differentiation. Overall design: Poly A purified total RNA was used for library construction using a method described by Parkhomchuk et. al. NAR 2009. The library was strand-specific but the pipeline for data analysis does not assume the library is strand-specific.
Publication Title
Chromatin signature of widespread monoallelic expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 62 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
bulk breast tumor RNA from patient
Publication Title
X chromosomal abnormalities in basal-like human breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples