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GSE74245
Mus musculus
8 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Metabolism in cancer serves to provide energy and key biomolecules that sustain cell growth, a process that is frequently accompanied by decreased mitochondrial use of glucose. Importantly, metabolic intermediates including mitochondrial metabolites are central substrates for post-translational modifications at the core of cellular signalling and epigenetics. However, the molecular means that coordinate the use of mitochondrial metabolites for anabolism and nuclear protein modification are poorly understood. Here, we unexpectedly found that genetic and pharmacological inactivation of Pyruvate Dehydrogenase A1 (PDHA1), a subunit of pyruvate dehydrogenase complex (PDC) that regulates mitochondrial metabolism16 inhibits prostate cancer development in different mouse and human xenograft tumour models. Intriguingly, we found that lipid biosynthesis was strongly affected in prostate tumours upon PDC inactivation. Mechanistically, we found that nuclear PDC controls the expression of Sterol regulatory element-binding transcription factor (SREBF) target genes by mediating histone acetylation whereas mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated effort to sustain anabolism. In line with the oncogenic function of PDC in prostate cancer, we find that PDHA1 and the PDC activator, Pyruvate dehydrogenase phospatase 1 (PDP1), are frequently amplified and overexpressed at both gene and protein level in these tumours. Taken together, our findings demonstrate that both mitochondrial and nuclear PDC sustains prostate tumourigenesis by controlling lipid biosynthesis thereby pointing at this complex as a novel target for cancer therapy.
Publication Title
Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Fetal and neonatal beta cells have poor glucose-induced insulin secretion and only gain robust glucose responsiveness several weeks after birth. This unresponsiveness may be due to a generalized immaturity of the metabolic pathways normally found in beta cells.
Publication Title
Rat neonatal beta cells lack the specialised metabolic phenotype of mature beta cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multiple gene expression studies have demonstrated that breast cancer biological diversity is associated with distinct transcriptional programs. Transcription factors, because of their unique ability to coordinate the expression of multiple genes, are speculated to play a role in generating phenotypic plasticity associated with cancer progression including acquired drug resistance. Combinatorial libraries of artificial zinc-finger transcription factors (ZF-TFs) provide a robust means for inducing and understanding various functional components of the cancer phenotype. Herein, we utilized combinatorial ZF-TF library technology to better understand how breast cancer cells acquire resistance to a fulvestrant, a clinically important anti-endocrine therapeutic agent. We isolated six ZF-TF library members capable of inducing stable, long-term anti-endocrine drug-resistance in two independent estrogen receptor positive breast cancer cell lines. Comparative gene expression profile analysis of the ZF-TF-transduced breast cancer cell lines revealed a 72-gene cluster that constituted a common signature for the fulvestrant-resistance phenotype. Pathway enrichment-analysis of gene expression data revealed that the ZF-TF-induced fulvestrant resistance is associated with an estrogen receptor negative-like gene set and four unique myb-regulated gene sets. Furthermore, we identified a set of genes strongly expressed in the ZF-TF-induced fulvestrant-resistant cells that was correlated with a lower probability of distant metastasis-free or death-from-relapse-free survival of breast cancer patients.
Publication Title
Induction of stable drug resistance in human breast cancer cells using a combinatorial zinc finger transcription factor library.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To assess pathologic complete response (pCR), clinical response, feasibility, safety, and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. EXPERIMENTAL DESIGN: 48 patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks. Single and multigene biomarker studies were done in an attempt to identify predictors of response. RESULTS: 8 of 40 (20%) patients achieved pCR (95% confidence interval, 9-36%). Of 9 additional patients recruited for protocol-defined toxicity analysis, 8 were evaluable; 42 of 48 (88%) patients had clinical response (16 patients, clinical complete response; 26 patients, clinical partial response). T(1) tumors more frequently exhibited clinical complete response (P = 0.05) and showed a trend to exhibit pCR (P = 0.07). 5 (13%) patients experienced grade 1 cardiac dysfunction during preoperative treatment. Neither HER2 nor estrogen receptor status changed significantly after exposure to trastuzumab and vinorelbine. RNA profiling identified three top-level clusters by unsupervised analysis. Tumors with extremes of response [pCR (n = 3) versus nonresponse (n = 3)] fell into separate groups by hierarchical clustering. No predictive genes were identified in pCR tumors. Nonresponding tumors were more likely to be T(4) stage (P = 0.02) and express basal markers (P < 0.00001), growth factors, and growth factor receptors. Insulin-like growth factor-I receptor membrane expression was associated with a lower response rate (50% vs 97%; P = 0.001). CONCLUSIONS: Preoperative trastuzumab plus vinorelbine is active and well tolerated in patients with HER2-positive, operable, stage II/III breast cancer. HER2-overexpressing tumors with a basal-like phenotype, or with expression of insulin-like growth factor-I receptor and other proteins involved in growth factor pathways, are more likely to be resistant to this regimen.
Publication Title
Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiScanSQ
Description
Purpose: Citron kinase (CitK) knockout mice show a severe form of primary microcephaly, associated with ataxia and lethal epilepsy. This phenotype is caused by massive apoptosis occuring during embryonic and post-natal brain development, associated with cytokinesis failure. Cerebellum is the tissue showing highest sensitivity to CitK loss. The clinical phenotype of CitK knockout mice is significantly resued by P53 inactivation. In addition, CitK/P53 double knockout brains have almost normal levels of apoptosis, but display high percentage of binucleated and multinucleated cells. The aim of this study was to analyze the gene expression changes produced in developing neural tissue by CitK loss and to determine which alterations are P53-dependent. expression changes Methods: We analyzed by RNA sequencing total RNA extracted from P4 cerebellum of mice characterized by the following genotypes: 1. CitK +/-, P53 +/- (CTRL); 2. CitK -/-, P53 +/- (CitK-KO); 3. CitK +/-, P53 -/- (P53-KO); 4. CitK -/-, P53 -/- (D-KO). Biological triplicates were analyzed per every genotype. Conclusions: The loss of CitK leads to a strong reduction of the expression of pro-neural genes and induces a P53-related pro-apoptotic gene sets. The analysis of D-KO mice reveals that most of these changes are P53-dependent, but many genes implicated in growth arrest are induced through P53-independent mechanisms. Overall design: Cerebellar mRNA profiles of 4-day old mice of CTRL, CitK-KO, P53-KO and D-KO mice were generated by deep sequencing, in triplicate, using Illumina HiScan SQ
Publication Title
ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 84 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Evidence suggests that BRCA1 mutation associated tumors have increased sensitivity to DNA damaging agents like cisplatin. Sporadic triple negative breast cancers (TNBC) have many phenotypic similarities to BRCA1 tumors and may have a similar sensitivity to cisplatin. We tested the efficacy of cisplatin monotherapy in 28 TNBC patients in a single arm neoadjuvant trial with outcome measured by pathologic treatment response quantified using the Miller-Payne scale.
Publication Title
Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer.
Sample Metadata Fields
Age, Disease stage
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
To identify novel therapeutic opportunities for patients with acquired resistance to endocrine treatments in breast cancer, we applied a high-throughput drug screen. The IC50 values were determined for MCF7 and MCF7-LTED cells.
Publication Title
VAV3 mediates resistance to breast cancer endocrine therapy.
Sample Metadata Fields
Cell line
View Samples- Zea mays
- 17 Downloadable Samples
- Illumina Genome Analyzer II
Description
We have generated over 80 million 32 nt reads generated from RNA samples isolated from the tip and base of a developing Mo17 leaf. A comparision of these data with the maize AGP resulted in the confirmation of approximately 88% of the maize filtered gene set Keywords: Transcriptome analysis Overall design: Examination of two different RNA samples from two different segments of a developing 3rd leaf
Publication Title
The B73 maize genome: complexity, diversity, and dynamics.
Sample Metadata Fields
Specimen part, Subject
View Samples- Zea mays
- 4 Downloadable Samples
- Illumina Genome Analyzer
Description
All above ground organs of higher plants are ultimately derived from shoot apical meristems (SAMs). The SAM exhibits distinctive structural organization, and monocot SAMs such as maize are comprised of two cell layers, a single cell layered tunica (L1) and a corpus (L2). Although recent research has revealed roles of these cell layers in the SAM, intra- and inter-cell-layer signaling networks involved in organ development remain largely unknown except for a few differentially expressed genes. Here, we used Illumnia technology to conduct RNA-seq of L1 and L2 cell layers in maize B73 maize shoot apical meristem. Overall design: Single sequencing library was constructed for L1 and L2 cell layer. Each library was sequenced using 2 lanes on a Solexa flow cell. Processed data file 'ZmB73_4a.53_filtered_genes.fasta' and its README file are linked below as supplementary files. The fasta file contains the gene model ID and corresponding sequence generated from maize genome project. This fasta file was used for the following samples: GSM418173, GSM418174, GSM420173, GSM420174, GSM422828, GSM422829.
Publication Title
The B73 maize genome: complexity, diversity, and dynamics.
Sample Metadata Fields
Age, Subject
View Samples- Zea mays
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
Heterosis (hybrid vigor) refers to the superior performance of hybrid progeny relative to their parents. Although widely exploited in agriculture, the mechanisms responsible for heterosis are not well understood. As a monoecious organism, a given maize plant can be used as both male and female parents of crosses. Regardless of the cross direction, the maize inbred lines B73 and Mo17 produce hybrids that substantially out-perform their parents. These reciprocal hybrids differ phenotypically from each other despite having identical nuclear genomes. Consistent with these phenotypic observations, 30-50% of genes were differentially expressed between these reciprocal hybrids. An eQTL experiment conducted to better understand the regulation of gene expression in inbred and hybrid lines detected ~4,000 eQTL associations. The majority of these eQTL act in trans to regulate expression of genes on other chromosomes. Surprisingly, many of the trans-eQTL, when heterozygous, differentially regulated transcript accumulation in a manner consistent with gene expression in the hybrid being regulated exclusively by the paternally transmitted allele. The design of the eQTL experiment controlled for cytoplasmic and maternal effects, suggesting that widespread paternal genomic imprinting contributes to the regulation of gene expression in maize hybrids. Keywords: eQTL, parent-of-origin Overall design: GPL4521 - SAM1.2 (Reciprocal Hybrid Comparison): Six replications of B73xMo17 and Mo17xB73 were grown in growth chambers to tightly control environmental variation. Seeds from each genotype were taken from a single source (ear) for all six replications. Within each replication, genotypes were randomly assigned growth locations. Six healthy seedlings for each genotype and replication were harvested at two weeks of age. For each replication, B73xMo17 and Mo17xB73 were hybridized to the SAM1.2 microarray (GPL4521) using a randomized, alternate dye assignment. GPL3333 - SAM1.1 and GPL3538 - SAM3.0 (eQTL Experiment): Four biological replications of the RIL, B73xRIL, and Mo17xRIL cross-types were planted in growth chambers using seed from a single source for each genotype. Each RIL and its crosses onto B73 and Mo17 were planted using a split-plot design with RIL group (RIL and its cross onto B73 and Mo17) as the whole-plot treatment factor and cross-type (RIL, B73xRIL, and Mo17xRIL) as the split-plot treatment factor. The whole-plot portion of the experiment was designed as a randomized complete block design with four replications carried out on four separate occasions in the same environment. For the split-plot portion of the design, twelve seedlings of each RIL and its crosses were randomized within two adjacent flats in a growth chamber (six healthy seedlings per genotype were randomly chosen and pooled at harvest). For each replication, RIL, B73xRIL, and Mo17xRIL cross-types were hybridized to custom cDNA microarrays using a loop design such that each loop included all pairwise comparisons between the RIL and its crosses with B73 and Mo17. Four biological replications were hybridized to the SAM1.1 (GPL3333) array and two of the four biological replications were hybridized to SAM3.0 (GPL3538). RNA samples were alternately labeled to provide dye balance within each loop and replication. GPL8734 - Gene Expression between two maize reciprocal hybrids Heterosis refers to the enhanced agronomic performance of a hybrid relative to its (usually) inbred parents. We have previously documented widespread differences in gene expression in the B73xMo17 hybrid relative to its inbred parents B73 and Mo17 (Swanson, et al., 2006, PNAS). The reciprocal B73xMo17 and Mo17xB73 hybrids are both highly heterotic, but despite having identical nuclear genomes exhibit statistically significant differences in multiple traits. RNA-seq experiment was conducted to compare the gene expression globally between the two reciprocal hybrids. 1 samples from B73XMo17 and Mo17XB73 RNAs were extracted from a single replication of 14-day-old B73xMo17 and Mo17xB73 seedlings. RNAs were purified using DNaseI treatment followed by cleanup with the RNeasy Plant Mini Kit (Qiagen, Valencia, CA) as per manufacturer instructions. Sequencing library construction was completed using the Illumina mRNA-Seq sample preparation kit. Processed data file 'ZmB73_4a.53_filtered_genes.fasta' and its README file are linked below as supplementary files. The fasta file contains the gene model ID and corresponding sequence generated from maize genome project. This fasta file was used for the following samples: GSM418173, GSM418174, GSM420173, GSM420174, GSM422828, GSM422829.
Publication Title
The B73 maize genome: complexity, diversity, and dynamics.
Sample Metadata Fields
Age, Specimen part
View Samples