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GSE56843
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SRC-1 affects the expression of complex I of the mitochondrial electron transport chain, a set of enzymes responsible for the conversion of NADH to NAD(+). NAD(+) and NADH were subsequently identified as metabolites that underlie SRC-1's response to glucose deprivation. Knockdown of SRC-1 in glycolytic cancer cells abrogated their ability to grow in the absence of glucose consistent with SRC-1's role in promoting cellular adaptation to reduced glucose availability
Publication Title
Steroid receptor coactivator 1 is an integrator of glucose and NAD+/NADH homeostasis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Although remission rates for metastatic melanoma are generally very poor, some patients can survive for prolonged periods following metastasis. We used gene expression profiling, mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions to search for a molecular basis for this observation and to develop improved methods for predicting patient survival. We identified a group of 266 genes associated with postrecurrence survival. Genes positively associated with survival were predominantly immune response related (e.g., ICOS, CD3d, ZAP70, TRAT1, TARP, GZMK, LCK, CD2, CXCL13, CCL19, CCR7, VCAM1) while genes negatively associated with survival were cell proliferation related (e.g., PDE4D, CDK2, GREF1, NUSAP1, SPC24).
Publication Title
Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aged STAT1-/- female mice spontaneously develop ERa+ PR+ mammary tumors that exhibit strikingly similar hormone-sensitivity and -dependency as human ERa+ luminal breast cancers.
Publication Title
STAT1-deficient mice spontaneously develop estrogen receptor α-positive luminal mammary carcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
Illumina HiSeq 2500
Description
RNA-sequencing of mRNA isolated from in vitro decidualizaing human endometrial stromal cells with or without siRNA-mediated knockdown of PLZF Overall design: Primary human endometrial stromal cells isolated from 3 healthy volunteers. Transfected with nontargeting or PLZF siRNA. Treated with estradiol, medroxyprogesterone acetate, and cAMP (EPC) for 0 or 3 days
Publication Title
Human endometrial stromal cell decidualization requires transcriptional reprogramming by PLZF.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Approximately 20% of early-stage breast cancers display amplification or overexpression of the ErbB2/HER2 oncogene, conferring poor prognosis and resistance to endocrine therapy. Targeting HER2+ tumors with trastuzumab or the receptor tyrosine kinase (RTK) inhibitor lapatinib significantly improves survival, yet tumor resistance and progression of metastatic disease can develop over time. While the mechanisms of cytosolic HER2 signaling are well studied, nuclear signaling components and gene regulatory networks that bestow therapeutic resistance and limitless proliferative potential are incompletely understood. Here, we use biochemical and bioinformatics approaches to identify effectors and targets of HER2 transcriptional signaling in human breast cancer. Phosphorylation and activity of the Steroid Receptor Coactivator-3 (SRC-3) is reduced upon HER2 inhibition, and recruitment of SRC-3 to regulatory elements of endogenous genes is altered. Transcripts regulated by HER2 signaling are highly enriched with E2F1 binding sites and define a gene signature associated with proliferative breast tumor subtypes, cell cycle progression, and G1 to S phase transition. We show that HER2 signaling drives proliferation in breast cancer cells through regulation of E2F1-driven DNA metabolism and replication genes together with phosphorylation and activity of the transcriptional coactivator SRC-3. Furthermore, our analyses identified a cyclin dependent kinase (CDK) signaling node that, when targeted using the CDK4/6 inhibitor Palbociclib, defines cooperative signaling pathways for expression of tumorigenic gene networks. Our findings suggest this proliferative gene signature is amendable to pharmacological targeting. These results have implications for rational discovery of pharmacological combinations in pre-clinical models of adjuvant treatment and therapeutic resistance
Publication Title
HER2 Signaling Drives DNA Anabolism and Proliferation through SRC-3 Phosphorylation and E2F1-Regulated Genes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mice have been treated with NOX-A12. Whole BM cells have been harvested, RNA isolated, and gene expression profiling was performed on cDNA using Mouse Genome 430 2.0 array. Untreated mice have been used as control.
Publication Title
SDF-1 inhibition targets the bone marrow niche for cancer therapy.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Similar to resting mature B cells, where the B-cell antigen receptor (BCR) is essential for cellular survival, surface BCR expression is conserved in most mature B cell lymphomas. The identification of activating BCR mutations and the growth disadvantage upon BCR knockdown of cells of certain lymphoma entities has led to the view that BCR signaling is required for tumour cell survival. Consequently, the BCR signaling machinery has become a new target in the therapy of B cell malignancies. Here, we studied the effects of BCR ablation on MYC-driven mouse B cell lymphomas and compared them to observations in human Burkitt lymphoma. Whereas BCR ablation did not, per se, significantly affect lymphoma growth, BCR-negative (BCR-) tumour cells rapidly disappeared in the presence of their BCR-expressing (BCR+) counterparts in vitro and in vivo. This required neither cellular contact, nor factors released by BCR+ tumour cells. Instead, BCR loss induced the rewiring of central carbon metabolism increasing the sensitivity of receptor-less lymphoma cells to nutrient restriction. The BCR attenuated GSK3 activity to support MYC-controlled gene expression. BCR- tumour cells exhibited increased GSK3 activity and were rescued from their competitive growth disadvantage by GSK3. BCR-negative lymphoma variants that restored competitive fitness, normalized GSK3 following constitutive activation of the MAPK pathway, commonly through Ras mutations. Similarly, in Burkitt lymphoma, activating RAS mutations may propagate Ig-crippled tumour cells, which usually represent a minority of the tumour bulk. Thus, while BCR expression enhances lymphoma cell fitness, BCR-targeted therapies may profit from combinations with drugs targeting BCR-less tumour cells.
Publication Title
The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS and non-ICRBS suggesting that different cis-acting regulatory functions are repressed by ZFP57 at these two classes of target loci. Overall, these data demonstrate that ZFP57 is pivotal to maintain the allele-specific epigenetic modifications of ICRs that in turn are necessary for maintaining the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet required. Overall design: Examination of mRNA levels in Zfp57-/- mouse ESCs compared to the wild-type.
Publication Title
ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The molecular mechanisms underlying the great differences in susceptibility to noise-induced hearing loss (NIHL) exhibited by both humans and laboratory animals are unknown. Using microarray technology, the present study demonstrates that the effects of noise overexposure on the expression of molecules likely to be important to the development of NIHL differ among inbred mice that have distinctive susceptibilities to NIHL including B6.CAST, 129X1/SvJ, and 129S1/SvImJ. The noise-exposure protocol produced, on average, a permanent loss of about 40 dB in sensitivity for auditory brainstem responses in susceptible B6.CAST mice, but no threshold elevations for the two resistant 129S1/SvImJ and 129X1/SvJ substrains. Measurements of noise-induced gene expression changes 6 h after the noise exposure revealed significant alterations in the expression levels of 48 genes in the resistant mice, while by these same criteria, there were seven differentially expressed genes in the susceptible B6.CAST mice. Differentially expressed genes in both groups of mice included subsets of transcription factors. However, only in the resistant mice was there a significant induction of proteins involved in cell-survival pathways such as HSP70, HSP40, p21, GADD45beta, Ier3, and Nf-kappaB. Moreover, increased expression of three of these factors after noise was confirmed at the protein level. Drastically enhanced HSP70, GADD45beta, and p21 immunostaining were detected 6 h after the noise exposure in subsets of cells of the lateral wall, spiral limbus, and organ of Corti as well as in cochlear nerve fibers. Upregulation of these proteins after noise exposure likely contributes to the prevalence of survival cellular pathways and thus to the resistance to NIHL that is characteristic of the 129X1/SvJ mice.
Publication Title
Noise-induced changes in gene expression in the cochleae of mice differing in their susceptibility to noise damage.
Sample Metadata Fields
No sample metadata fields
View Samples