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GSE50695
Homo sapiens
37 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer that is frequently associated with favorable outcomes, as ~90% of ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest that ILC patients receiving adjuvant endocrine therapy may not benefit from improved outcomes versus other breast cancer patients. Based on these observations, we characterized ER function and endocrine response in ILC models. The ER-positive ILC cell lines MDA MB 134VI (MM134) and SUM44PE were used to examine the ER-regulated transcriptome in vitro via gene expression microarray analyses and ER ChIP-Seq. In parallel, estrogen response was assessed in vivo in the patient-derived ILC xenograft HCI-013. Response to endocrine therapy was also examined in ILC cell lines. We identified 915 genes that were uniquely E2-regulated in ILC cell lines versus other breast cancer cell lines, and a subset of these genes were also regulated in vivo in HCI-013. We observed that MM134 were de novo tamoxifen resistant, and were induced to grow by 4-hydroxytamoxifen, as well as other anti-estrogens, as partial agonists. Growth was accompanied by agonist activity of tamoxifen on ER-mediated gene expression. Though tamoxifen induced cell growth, MM134 cells required FGFR1 signaling to maintain viability and were sensitive to combined endocrine therapy and FGFR1 inhibition. Our observation that ER drives a unique program of gene expression in ILC cells correlates with the ability of tamoxifen to induce growth in these cells. Targeting growth factors using FGFR1 inhibitors may block survival pathways required by ILC and reverse tamoxifen resistance.
Publication Title
Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer that is frequently associated with favorable outcomes, as ~90% of ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest that ILC patients receiving adjuvant endocrine therapy may not benefit from improved outcomes versus other breast cancer patients. Based on these observations, we characterized ER function and endocrine response in ILC models. The ER-positive ILC cell lines MDA MB 134VI (MM134) and SUM44PE were used to examine the ER-regulated transcriptome in vitro via gene expression microarray analyses and ER ChIP-Seq. In parallel, estrogen response was assessed in vivo in the patient-derived ILC xenograft HCI-013. Response to endocrine therapy was also examined in ILC cell lines. We identified 915 genes that were uniquely E2-regulated in ILC cell lines versus other breast cancer cell lines, and a subset of these genes were also regulated in vivo in HCI-013. We observed that MM134 were de novo tamoxifen resistant, and were induced to grow by 4-hydroxytamoxifen, as well as other anti-estrogens, as partial agonists. Growth was accompanied by agonist activity of tamoxifen on ER-mediated gene expression. Though tamoxifen induced cell growth, MM134 cells required FGFR1 signaling to maintain viability and were sensitive to combined endocrine therapy and FGFR1 inhibition. Our observation that ER drives a unique program of gene expression in ILC cells correlates with the ability of tamoxifen to induce growth in these cells. Targeting growth factors using FGFR1 inhibitors may block survival pathways required by ILC and reverse tamoxifen resistance.
Publication Title
Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 48 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: Transcriptome analysis of ESR1 mutant cells was performed via sequencing total RNA in T47D and MCF7 cell lines containing Y537S and D538G mutations. Overall design: Methods: Individual ESR1 WT and mutant T47D and MCF7 clones were hormone deprived in CSS for three days, pooled, and plated in quadruplicates in 6-well plates. The cells were treated with veh or 1nM E2 for 24 hrs, RNA was isolated and subjected to sequencing. Differential expression analysis was performed by DEseq2 and R was used to conduct statistical analysis tests
Publication Title
Mutation site and context dependent effects of ESR1 mutation in genome-edited breast cancer cell models.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 1000
Description
We constructed a polycistronic lentiviral vector to overexpress 3 germ cell specific genes (Stella, Oct4 and Nanos2) in mouse embryonic fibroblast (MEFs) and evaluated the transcriptome portrait in partially reprogrammed cells.We sequenced RNA samples from bulk cell population of two biological duplicates of MEF-GFP (control) and MEF-SON (overexpressed) 21 days post infection. Differential expression analysis of 50 M pair-end read per samples showed overexpression of neurogenesis, blood vessel and proliferation related genes and downregulation of chondroitin sulphate metabolic process, nitric oxide production and innate immune response genes. Overall design: Examination of whole transcriptome following concurrent overexpression of Stella, Oct4 and Nanos2 in MEFs.
Publication Title
Suppression of dsRNA response genes and innate immunity following Oct4, Stella, and Nanos2 overexpression in mouse embryonic fibroblasts.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chemotherapy may cause DNA damage within the oral mucosa of cancer patients leading to mucositis, a dose-limiting side effect for effective cancer treatment.
Publication Title
Microarray analyses of oral punch biopsies from acute myeloid leukemia (AML) patients treated with chemotherapy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 72 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
A data set of normal epithelium, serous ovarian surface epithelial-stromal tumors (benign and type II malignancies), stroma distal to tumor, and stroma adjacent to tumor (50 samples total). Additional cel files are included which represent replicate sampling from patients, and cel files that failed quality control but may be bioinformatically interesting. Additional replicate or failed cel files were not included in the final analysis (and so these samples were not included in the matrix).
Publication Title
Dysregulation of AKT3 along with a small panel of mRNAs stratifies high-grade serous ovarian cancer from both normal epithelia and benign tumor tissues.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: The study of human lacrimal gland biology and development is limited. Lacrimal gland tissue is damaged or poorly functional in a number of disease states including dry eye disease. Development of cell based therapies for lacrimal gland diseases requires a better understanding of the gene expression and signaling pathways in lacrimal gland. Differential gene expression analysis between lacrimal gland and other embryologically similar tissues may be helpful in furthering our understanding of lacrimal gland development. Methods: We performed global gene expression analysis of human lacrimal gland tissue using Affymetrix gene expression arrays. Primary data from our laboratory was compared with datasets available in the NLM GEO database for other surface ectodermal tissues including salivary gland, skin, conjunctiva and corneal epithelium. Results: The analysis revealed statistically significant difference in the gene expression of lacrimal gland tissue compared to other ectodermal tissues. The lacrimal gland specific, cell surface secretory protein encoding genes and critical signaling pathways which distinguish lacrimal gland from other ectodermal tissues are described. Conclusions: Differential gene expression in human lacrimal gland compared with other ectodermal tissue types revealed interesting patterns which may serve as the basis for future studies in directed differentiation among other areas.
Publication Title
Human Lacrimal Gland Gene Expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Alternative splicing comprises a robust generator of mammalian transcriptome complexity. Splice site specification and activity are controlled by interactions of cis-acting determinants on a transcript with specific RNA binding proteins. A major subset of these interactions comprises interactions localized to the intronic U-rich polypyrimidine tract located immediately 5’ to the majority of splice acceptors. alphaCPs (also referred to as polyC-binding proteins (PCBPs) and hnRNP Es) comprise a subset of KH-domain proteins with high specificity and affinity for C-rich polypyrimidine motifs. Prior studies have revealed that binding of alphaCPs to C-rich motifs can modulate splicing and 3’ processing of the human alpha-globin mRNA transcript in the nucleus as well as stabilization of the halpha-globin mRNA in the cytoplasm. In the current report, we demonstrate that alphaCPs have a positive impact on the activity of splice acceptor sites in a defined subset of mammalian transcripts via binding to polypyrimidine tracts that are predominantly C-rich. These findings lead us to conclude that the alphaCPs play a global role in determining the splicing activity and levels of cassette exon inclusion within the mammalian transcriptome. Overall design: To test the impact of aCP proteins on alternative splicing, aCP proteins were knockdown from K562 cells by siRNA. Since aCP1 and aCP2 have redundent function, we therefore designed siRNAs capable of knockdown both isoform at the same time. 3 aCP1/2 combined knockdown and 3 control siRNA knockdown were performed in K562 cells. RNA-seq were then performed to identify alternative splicing pattern mediated by aCP proteins.
Publication Title
αCP binding to a cytosine-rich subset of polypyrimidine tracts drives a novel pathway of cassette exon splicing in the mammalian transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
VSMC-specific MT1-MMP gene targeting in APOE-null mice promotes atherosclerosis and iliac artery aneurysm formation. To determine the MT1-MMP-dependent regulation of VSMC function, whole-genome transcriptomes of wild-type and MT1-MMP-null APOE-null VSMCs were determined.
Publication Title
Membrane-Tethered Metalloproteinase Expressed by Vascular Smooth Muscle Cells Limits the Progression of Proliferative Atherosclerotic Lesions.
Sample Metadata Fields
Specimen part
View Samples