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Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study was performed to check that ESR1 and BMI1 are biologically active after lentiviral transduction of primary human mammary epithelial cells (HMECs) with lentiviral vectors expressing ESR1 and BMI1 from the human PGK promoter. ESR1 targets like PGR, PRLR and GREB1, but not TFF1 and XBP1, were induced by estradiol in the ESR1-expressing cells. BMI1 targets like BMI1, NEFL and CCND2 were repressed in the BMI1-expressing cells. BMI1 suppressed genes associated with squamous and neural differentiation in the ESR1 plus BMI1-expressing cells.
Publication Title
An oestrogen-dependent model of breast cancer created by transformation of normal human mammary epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A high percentage of potential oncology drugs fail in clinical trials, partly because preclinical models used to test them are inadequate. Breast cancer is the leading cause of cancer-related death among women worldwide but we lack appropriate in vivo models for the ER+ subtypes, which represent more than 75% of all cases. We address these issues by xenografting tumor cells to their site of origin, the milk ducts. All ER+ cell lines and patient-derived xenografts grow mimicking their clinical counterparts. Disease progresses with invasion and metastasis, which become amenable to study. The action of hormones, important in breast carcinogenesis, can now be studied in a relevant context. Importantly, these open opportunities for development and evaluation of therapies.
Publication Title
A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A high percentage of potential oncology drugs fail in clinical trials, partly because preclinical models used to test them are inadequate. Breast cancer is the leading cause of cancer-related death among women worldwide but we lack appropriate in vivo models for the ER+ subtypes, which represent more than 75% of all cases. We address these issues by xenografting tumor cells to their site of origin, the milk ducts. All ER+ cell lines and patient-derived xenografts grow mimicking their clinical counterparts. Disease progresses with invasion and metastasis, which become amenable to study. The action of hormones, important in breast carcinogenesis, can now be studied in a relevant context. Importantly, these open opportunities for development and evaluation of therapies.
Publication Title
A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Estrogens and progesterone control mammary gland development and breast carcinogenesis via their cognate receptors expressed in a subset of cells of the luminal layer of the mammary epithelium. The extracellular matrix (ECM) including the basement membrane (BM) is important in breast physiology and tumorigenesis but how epithelial hormone receptor signaling and ECM are linked mechanistically is unclear. We identify the secreted protease Adamts18 as critical intermediary. Luminal estrogen and progesterone receptor signaling via upregulation of Wnt4 expression and ensuing canonical Wnt signaling activation in basal cells control Adamts18 expression there. The protease has an epithelial-intrinsic role in stem cell activation. We identify multiple binding partners in the interstitial ECM and BM and show that ADAMTS18 cleaves fibronectin in vitro. Its deletion results in increased fibronectin, collagen I and IV, and laminin deposition in pubertal glands. Adamts18 interacts genetically with Col18a1, which encodes a proteoglycan that is BM-specific, in stem cell regulation. Adamts18 inactivation impairs Hippo signaling and reduces Fgfr2 expression and signaling, which are vital for stem cell function. Our findings link epithelial hormone signaling to BM remodeling by Adamts18, and define the BM as an essential stem cell niche component.
Publication Title
The secreted protease Adamts18 links hormone action to activation of the mammary stem cell niche.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE1561- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
EORTC 10994 is a phase III clinical trial comparing FEC with ET in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 100 ng total RNA per chip were amplified using the Affymetrix small sample protocol (IVT then Enzo). 49 tumours were tested on Affymetrix U133A chips. The CEL files were quantile normalised together using rma. Clinical response data are not available yet.
Publication Title
Identification of molecular apocrine breast tumours by microarray analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
IlluminaHiSeq2500
Description
Senescence of stromal fibroblasts has been linked to establishment of cancer associated fibroblasts (CAF) and aging-associated increase of tumors. However, in clinically occurring carcinomas, density and proliferation of CAFs are frequently increased rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-J? in skin dermal fibroblasts is sufficient for CAF activation with consequent development of multifocal keratinocyte tumors. We now show that CSL deletion or knockdown induces senescence of primary fibroblasts derived from dermis, oral mucosa, breast and lung. CSL functions in these cells as a constitutive direct repressor of multiple senescence- and CAF-effector genes. At the same time, it physically interacts with p53, repressing its activity, and p53 activation provides a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblast senescence, enhances expression of CAF effector genes and, in vivo, promotes tumour and stromal cell expansion. Together, the findings support a CAF activation/stromal evolution model under convergent CSL/p53 control. Overall design: Human Dermal Fibroblasts were transfected with two different siRNA against CSL in parallel with a control siRNA. Total RNA was extracted 3 days post-transfection, followed by RNA-Seq analysis.
Publication Title
Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Senescence of stromal fibroblasts has been linked to establishment of cancer associated fibroblasts (CAF) and aging-associated increase of tumors. However, in clinically occurring carcinomas, density and proliferation of CAFs are frequently increased rather than decreased. We previously showed that genetic deletion or down-modulation of the canonical Notch effector CSL/RBP-J-kappa in skin dermal fibroblasts is sufficient for CAF activation with consequent development of multifocal keratinocyte tumors. We now show that CSL deletion or knockdown induces senescence of primary fibroblasts derived from dermis, oral mucosa, breast and lung. CSL functions in these cells as a constitutive direct repressor of multiple senescence- and CAF-effector genes. At the same time, it physically interacts with p53, repressing its activity, with p53 activation providing a failsafe mechanism against compromised CSL function. Concomitant loss of CSL and p53 overcomes fibroblasts senescence, enhances CAF effector gene expression and, in vivo, promotes stromal and cancer cell expansion. Together, these findings support a CAF activation/stromal evolution model under convergent CSL/p53 control.
Publication Title
Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation.
Sample Metadata Fields
Specimen part
View Samples SRP121892- Gallus gallus
- 7 Downloadable Samples
- Illumina HiSeq 2000
Description
Embryonic chicken telencephalon nuclei were isolated for RNAseq to identify transcripts differentially expressed across different brain regions.
Publication Title
Neocortical Association Cell Types in the Forebrain of Birds and Alligators.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Neuronal function critically depends on coordinated subcellular distribution of mRNAs. Disturbed mRNA processing and axonal transport has been found in spinal muscular atrophy and could be causative for dysfunction and degeneration of motoneurons. Despite the advances made in characterizing the transport mechanisms of several axonal mRNAs, an unbiased approach to identify the axonal repertoire of mRNAs in healthy and degenerating motoneurons has been lacking. Here we used compartmentalized microfluidic chambers to investigate the somatodendritic and axonal mRNA content of cultured motoneurons by microarray analysis. In axons, transcripts related to protein synthesis and energy production were enriched relative to the somatodendritic compartment. Knockdown of Smn, the protein deficient in spinal muscular atrophy, produced a large number of transcript alterations in both compartments. Transcripts related to immune functions, including MHC class I genes, and with roles in RNA splicing were upregulated in the somatodendritic compartment. On the axonal side, transcripts associated with axon growth and synaptic activity were downregulated. These alterations provide evidence that subcellular localization of transcripts with axonal functions as well as regulation of specific transcripts with nonautonomous functions is disturbed in Smn-deficient motoneurons, most likely contributing to the pathophysiology of spinal muscular atrophy.
Publication Title
Subcellular transcriptome alterations in a cell culture model of spinal muscular atrophy point to widespread defects in axonal growth and presynaptic differentiation.
Sample Metadata Fields
Specimen part
View Samples