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GSE84894
Caenorhabditis elegans
6 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Our understanding of cellular mechanisms by which animals regulate their response to starvation is limited despite the close relevance of the problem to major human health issues. L1 diapause of Caenorhabditis elegans, where newly hatched first stage larval arrested in response to food-less environment, is an excellent system to study the problem. We found through genetic manipulation and lipid analysis that ceramide biosynthesis, particularly those with longer fatty acid side chains, critically impacts animal survival during L1 diapause. Genetic and expression analyses indicate that ceramide likely regulate this response by affecting gene expression and activity in multiple regulatory pathways known to regulate starvation-induced stress, including the insulin-IGF-1 signaling (IIS) pathway, Rb and other pathways that mediate pathogen/toxin/oxidative stress responses. These findings provide an important insight into the roles of sphingolipid metabolism in not only starvation response but also aging and food-response related human health problems.
Publication Title
Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Ovis aries
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
To investigate the molecular bases of diet induced differences in milk composition, we collected milk from mid lactation dairy ewes and after 3 weeks of diet supplementation with extruded linseed. RNAs were isolated from milk somatic cells isolated from milk of 3 sheep and Illumina RNA sequencing was performed to analyze RNA synthesis in these cells. Overall design: Transcriptional profiling of milk somatic cells of sheep fed with normal diet and with a supplementation with extruded linseed. Sequence data were generated by deep sequencing, on three replicates, using Illumina HiSeq2000.
Publication Title
Transcript profiling in the milk of dairy ewes fed extruded linseed.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Primary effusion lymphoma is an aggressive B-cell lymphoma most commonly diagnosed in HIV-positive patients and universally associated with Kaposis sarcoma-associated herpesvirus (KSHV). Chemotherapy treatment of PEL yields only short-term remissions in the vast majority of patients yet efforts to develop superior therapeutic approaches have been impeded by lack of animal models that more accurately mimic human disease. To address this issue we developed a direct xenograft model, UM-PEL-1, by transferring freshly-isolated human PEL cells into the peritoneal cavities of NOD/SCID mice without in vitro cell growth. We utilized this model to show that bortezomib induces PEL remission and extends overall survival of mice bearing lymphomatous effusions. Transcriptome analysis by genomic arrays revealed that bortezomib downregulated cell cycle progression, DNA replication, and Myc-target genes.
Publication Title
Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.
Publication Title
Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
One-third of all ER+ breast tumors treated with endocrine therapy fail to respond, and the remainder are likely to relapse in the future. Almost all data on endocrine resistance has been obtained in models of invasive ductal carcinoma (IDC). However, invasive lobular carcinomas (ILC) comprise up to 15% of newly diagnosed invasive breast cancers diagnosed each year and, while the incidence of IDC has remained relatively constant during the last 20 years, the prevalence of ILC continues to increase among postmenopausal women. We report a new model of Tamoxifen (TAM)-resistant invasive lobular breast carcinoma cells that provides novel insights into the molecular mechanisms of endocrine resistance. SUM44 cells express ER and are sensitive to the growth inhibitory effects of antiestrogens. Selection for resistance to 4-hydroxytamoxifen led to the development of the SUM44/LCCTam cell line, which exhibits decreased expression of estrogen receptor alpha (ER) and increased expression of the estrogen-related receptor gamma (ERR). Knockdown of ERR in SUM44/LCCTam cells by siRNA restores TAM sensitivity, and overexpression of ERR blocks the growth-inhibitory effects of TAM in SUM44 and MDA-MB-134 VI lobular breast cancer cells. ERR-driven transcription is also increased in SUM44/LCCTam, and inhibition of activator protein 1 (AP1) can restore or enhance TAM sensitivity. These data support a role for ERR/AP1 signaling in the development of TAM resistance, and suggest that expression of ERR may be a marker of poor Tamoxifen response.
Publication Title
ERRgamma mediates tamoxifen resistance in novel models of invasive lobular breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial lineage cells generated a cell (mECK36) that induced KS-like tumors in mice. mECK36 formed KSHV-harboring vascularized spindle-cell sarcomas that were LANA+ and displayed a KSHV and host transcriptomes reminiscent of KS tumors.
Publication Title
In vivo-restricted and reversible malignancy induced by human herpesvirus-8 KSHV: a cell and animal model of virally induced Kaposi's sarcoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
A major barrier to research on Parkinsons disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding -synuclein. -Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double -synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of -synuclein, and for mechanistic experiments to study PD pathogenesis.
Publication Title
Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A major barrier to research on Parkinsons disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding -synuclein. -Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double -synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of -synuclein, and for mechanistic experiments to study PD pathogenesis.
Publication Title
Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus.
Sample Metadata Fields
Specimen part, Cell line
View Samples