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Homo sapiens
30 Downloadable Samples
IlluminaHiSeq2000
Description
Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) – the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR. This insight led to the development of the AR antagonist enzalutamide. However, resistance to enzalutamide invariably develops, and disease progression is nearly universal. One mechanism of resistance to enzalutamide is an F877L mutation in the AR ligand-binding domain that can convert enzalutamide to an agonist of AR activity. However, mechanisms that contribute to the agonist switch had not been fully clarified, and there were no therapies to block AR F877L. Using cell line models of castration-resistant prostate cancer (CRPC), we determined that cellular androgen content influences enzalutamide agonism of mutant F877L AR. Further, enzalutamide treatment of AR F877L-expressing cell lines recapitulated the effects of androgen activation of F877L AR or wild-type AR. Because the BET bromodomain inhibitor JQ-1 was previously shown to block androgen activation of wild-type AR, we tested JQ-1 in AR F877L-expressing CRPC models. We determined that JQ-1 suppressed androgen or enzalutamide activation of mutant F877L AR and suppressed growth of mutant F877L AR CRPC tumors in vivo, demonstrating a new strategy to treat tumors harboring this mutation. Overall design: RNA-seq profiles of prostate cancer cell lines to understand gene expression associated with enzalutamide treatment
Publication Title
Cellular androgen content influences enzalutamide agonism of F877L mutant androgen receptor.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 8 Downloadable Samples
Affymetrix Rat Genome U34 Array (rgu34a)
Description
To examine changes in gene expression that might occur in CNS glial cells in response to the secreted products of immune cells, we used gene array analysis to assess the early effects of different cytokine mixtures on rat mixed CNS glia in culture. We compared effects at 6 hours of cytokines typical of Th1 and Th2 lymphocytes, and monocyte marophages (M/M).. We found unique patterns of changes in gene expression for each of the three cytokine mixtures, including changes in immune-related molecules, neurotrophins, growth factors, proteins involved in axon/glial interactions, ion channels, neurotransmitters, mitochondrial function and apoptosis. These changes may have relevance in neuroprotective or damaging mechanisms in neurodegenerative diseases such as multiple sclerosis, specifically with regard to formation, repair or inhibition of lesion formation.
Publication Title
Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ovariectomized virgin Ccnd1-/- and Ccnd1+/+ mice (5 weeks of age) were allowed to recuperate for 2 weeks. The mice were assigned to either replacement pellets containing E2 (0.75 mg, 60-day release) or pellet containing placebo. Mice were sacrificed at day 7 after pellet implantation. RNA extracted from mammary glands (3 each group) was labeled and used to probe Affymetrix 430_2.0 arrays.
Publication Title
Cyclin D1 determines estrogen signaling in the mammary gland in vivo.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The CCND1 gene, which is frequently overexpressed in cancers, encodes the regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma protein (pRb). It is known that cyclin D1 regulates ER transactivation using heterologous reporter systems, the significance of this observation to E2 dependent gene activation is unknow. E2 stimulated MCF7 cells treated with cyclin D1 siRNA in order to analyze the genes regulated by estradiol in a cyclin D1 dependent manner. Hormone deprived MCF7 cells were treated with cyclin D1 siRNA or control siRNA and stimulated with E2 or vehicle
Publication Title
Cyclin D1 determines estrogen signaling in the mammary gland in vivo.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Murine prostate epithelial cells (PECs) were obtained from Ccnd1-/- and Ccnd1+/+ FvB mice (2-3 months of age). RNA extracted from PECs (3 technical replicates for each group) was labeled and used to probe Affymetrix 430_2.0 arrays.
Publication Title
Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE10849- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hearts Lacking Caveolin-1 Develop Hypertrophy with Normal Cardiac Substrate Metabolism
Publication Title
Hearts lacking caveolin-1 develop hypertrophy with normal cardiac substrate metabolism.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Mitochondria control bioenergetics and cell fate decisions, but whether they also participate in extra-organelle signaling is not understood. Here, we show that interference with cyclophilin D (CypD), a mitochondrial matrix protein and apoptosis regulator, causes accelerated cell proliferation and enhanced cell migration and invasion. These responses are associated with global transcriptional changes in CypD-/- cells, predominantly affecting chemokines and their receptors, and resulting in increased activating phosphorylation of Signal Transduction and Activator of Transcription 3 (STAT3). In turn, STAT3 signaling promotes increased proliferation of CypD-/- cells via accelerated S-phase entry and supports Cxcl12-directed paracrine cell motility. Therefore, mitochondria-to-nuclei transcriptional signaling globally affects cell division and motility. As immunosuppressive therapies often target CypD, this pathway may predispose the tissue microenvironment of these patients to oncogenic transformation.
Publication Title
Cyclophilin D extramitochondrial signaling controls cell cycle progression and chemokine-directed cell motility.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), (imblegenhumandnamethylation2.1mdeluxepromoterarray[100929hg19deluxeprommethhx1)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenetic mechanisms underlying arsenic-associated lung carcinogenesis.
Sample Metadata Fields
Specimen part, Disease, Treatment, Time
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Arsenic is methylated during its metabolism, thereby depleting the intracellular methyl donor S-adenosyl-methionine, which may lead to disturbances in DNA methylation patterns which could lead to altered gene expression
Publication Title
Epigenetic mechanisms underlying arsenic-associated lung carcinogenesis.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Here, we show that functional loss of a single gene is sufficient to confer constitutive milk protein production and protection against mammary tumor formation. Caveolin-3 (Cav-3), a muscle-specific caveolin-related gene, is highly expressed in striated and smooth muscle cells. We demonstrate that Cav-3 is also expressed in myoepithelial cells within the mammary gland. To determine if genetic ablation of Cav-3 expression affects adult mammary gland development, we next studied the phenotype(s) of Cav-3 (-/-) null mice. Interestingly, detailed analysis of Cav-3 (-/-) virgin mammary glands shows dramatic increases in ductal thickness, side-branching, and the development of extensive lobulo-alveolar hyperplasia, akin to the changes normally observed during pregnancy and lactation. Analysis by genome-wide expression profiling reveals the upregulation of gene transcripts associated with pregnancy/lactation, mammary stem cells, and human breast cancers, consistent with a constitutive lactogenic phenotype. The expression levels of three key transcriptional regulators of lactation, namely Elf5, Stat5a, and c-Myc are also significantly elevated. Experiments with pregnant mice directly show that Cav-3 (-/-) mice undergo precocious lactation. Finally, using orthotopic implantation of a transformed mammary cell line (known as Met-1), we demonstrate that virgin Cav-3 (-/-) mice are dramatically protected against mammary tumor formation. Interestingly, Cav-3 (+/-) mice also show similar protection, indicating that even reductions in Cav-3 levels are sufficient to render these mice resistant to tumorigenesis. Thus, Cav-3 (-/-) mice are a novel preclinical model to study the protective effects of a constitutive lactogenic microenviroment on mammary tumor onset and progression. Our current studies have broad implications for using the lactogenic micro-environment as a paradigm to discover new therapies for the prevention and/or treatment of human breast cancers. Most importantly, a lactation-based therapeutic strategy would provide a more natural and nontoxic approach to the development of novel anti-cancer therapies.
Publication Title
Loss of caveolin-3 induces a lactogenic microenvironment that is protective against mammary tumor formation.
Sample Metadata Fields
No sample metadata fields
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