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GSE35428
Homo sapiens
106 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study, we have utilized microarray analysis to directly compare a subset of structurally distinct, clinically relevant SERMs in the presence and absence of estradiol, using a high replicate number (10) to ensure detection of modestly regulated genes.
Publication Title
Research resource: Transcriptional profiling in a cellular model of breast cancer reveals functional and mechanistic differences between clinically relevant SERM and between SERM/estrogen complexes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
We report that decreased expression and activity of AhR exacerbates murine neovascular age-related macular degeneration, and increases cell migration and tube formation. The mechanism involves increased expression of pro-angiogenic mediators and altered matrix degradation. The results of our study suggest that the AhR signaling pathway may be important in multiple AMD related pathways. Overall design: Gene expression analysis in the retinal pigment epithelium (RPE)-choroid tissue from AhR knockout mice contrasted against wild-type age-matched controls.
Publication Title
Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This dataset is part of the manuscript titled "The metabolic regulator ERRalpha, a downstream target of HER2/IGF1, as a therapeutic target in breast cancer" (in review). The expression data obtained in human mammary epithelial cells were used to generate a list of ERRalpha-regulated genes that was later refined in clinical breast cancer datasets to generate a clinically relevant signature of ERalpha activity (referred to as Cluster 3 signature). Using this signature of the estrogen-related receptor alpha (ERRa) to profile more than eight-hundred breast tumors, we found that patients with tumors exhibiting higher ERRa activity were predicted to have shorter disease free survival. Further, the ability of an ERRa antagonist, XCT790, to inhibit breast cancer cell proliferation correlates with the cells intrinsic ERRa activity. These findings highlight the potential of using the ERRa signature and antagonists in targeted therapy for breast cancer. Using a chemical genomic approach we determined that activation of the HER2/IGF1 signaling pathways upregulates the expression of PGC-1b, an obligate cofactor for ERRa activity. Knockdown of PGC-1b in HER2 positive breast cancer cells impaired ERRa signaling and reduced cell proliferation, implicating a functional role of PGC1b/ERRa in the pathogenesis HER2 positive breast cancer.
Publication Title
The metabolic regulator ERRα, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The goal of this study was to determine the effects of a well-characterized anti-androgen, abiraterone acetate, and a suspected human anti-androgen, di-n-butyl phthalate (DBP) on the androgenic function of human fetal testis. Human fetal testis was xenografted into the renal subcapsular space of castrated male athymic nude mice. Hosts were treated with hCG to stimulate testosterone production in the xenografts, and were concurrently treated with either abiraterone acetate or DBP. While abiraterone acetate (14 d, 75 mg/kg/d p.o.) dramatically reduced testosterone and the weights of androgen-sensitive host organs, DBP (14 d, 500 mg/kg/d p.o.) had no effect on androgenic endpoints.
Publication Title
Differential response to abiraterone acetate and di-n-butyl phthalate in an androgen-sensitive human fetal testis xenograft bioassay.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Orphan nuclear receptor estrogen-related receptor alpha (ERR) has recently been shown to carry negative prognostic significance in breast and ovarian cancers. The specific role of ERR in tumor growth and progression, however, is yet to be fully understood. The significant homology between estrogen receptor alpha (ER) and ERR initially suggested that these receptors may share similar transcriptional targets. Using the well-characterized ER-positive MCF-7 breast cancer cell line, we sought to gain a genome-wide picture of ER-ERR cross-talk using an unbiased microarray approach.
Publication Title
Estrogen-related receptor alpha is critical for the growth of estrogen receptor-negative breast cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Both pro- and anti-mitogenic activities have been ascribed to progesterone receptor (PR) agonists and antagonists in breast cancer cells, however, the transcriptional responses that underlie these paradoxical functions are not apparent. Using non-transformed, normal human mammary epithelial cells (hMECs) engineered to express PR, and standard microarray technology, we defined 2,370 genes that were significantly regulated by the PR agonist R5020. Gene Ontology (GO) analysis revealed that GO-terms involved in inflammation and NF-B signaling were among the most significantly regulated. Interestingly, on those NF-B responsive genes that were inhibited by agonist-activated PR, antagonists either (a) mimicked the actions of agonists or (b) reversed the inhibitory actions of agonists. This difference in pharmacological response could be attributed to the fact that although agonist and antagonist-activated PR is recruited to the promoters of NF-B responsive promoters, the physical presence of PR tethered to the promoter of some genes is sufficient for transcriptional inhibition whereas on others an agonist-activated PR conformation is required for inhibition of NF-B signaling. Importantly, the actions of PR on the latter class of genes were reversed by an AF-2 inhibiting, LXXLL-containing peptide. Consideration of the relative activities of these distinct anti-inflammatory pathways in breast cancer may be instructive with respect to the likely therapeutic activity of PR agonists or antagonists in the treatment of breast cancer.
Publication Title
Mechanisms of progesterone receptor inhibition of inflammatory responses in cellular models of breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We have previously identified a family of novel androgen receptor (AR) ligands that, upon binding, enable AR to adopt structures distinct from that observed in the presence of canonical agonists. In this report, we describe the use of these compounds to establish a relationship between AR structure and biological activity with a view to defining a rational approach with which to identify useful Selective Androgen Receptor Modulators (SARMs). As one of the approaches, we used a DNA microarray analysis to demonstrate that differently conformed receptors facilitate distinct patterns of gene expression in LNCaP cells. Interestingly, we observed a complete overlap in the identity of genes expressed following treatment with mechanistically distinct AR ligands. However, it was differences in the kinetics of gene regulation that distinguished these compounds. Follow-up studies, in cell-based assays of AR action, confirmed the importance of these alterations in gene expression. Together these studies demonstrate an important link between AR structure, gene expression and biological outcome.
Publication Title
Linking ligand-induced alterations in androgen receptor structure to differential gene expression: a first step in the rational design of selective androgen receptor modulators.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PGC-1 transcription factor was customized to limit its interations to ERRalpha. This mutant (2x9) was used to dissect the transcription activation patterns that are attributable to the PGC1-ERR interaction and PGC-1 actions that are independent of ERR. Inactive mutant with the deleted LLXXL motifs (L2L3) and wt PGC-1 were used as negative and positive controls respectively. BGAL-expressing construct was used to control for non-specific effects of adenoviral infection.
Publication Title
Receptor-selective coactivators as tools to define the biology of specific receptor-coactivator pairs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 90 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Background: Expression level of many genes shows abundant natural variation in human populations. The variations in gene expression are believed to contribute to phenotypic differences. Emerging evidence has shown that microRNAs (miRNAs) are one of the key regulators of gene expression. However, past studies have focused on the miRNA target genes and use loss- or gain-of-function approach that may not reflect natural association between miRNA and mRNAs. Methodology/Principal Findings: To examine miRNA regulatory effect on global gene expression under endogenous condition, we performed pair-wise correlation coefficient analysis on expression levels of 366 miRNAs and 14,174 messenger RNAs (mRNAs) in 90 immortalized lymphoblastoid cell lines, and observed significant correlations between the two species of RNA transcripts. We identified a total of 7,207 significantly correlated miRNA-mRNA pairs (false discovery rate q <0.01). Of those, 4,085 pairs showed positive correlations while 3,122 pairs showed negative correlations. Gene ontology analyses on the miRNA-correlated genes revealed significant enrichments in several biological pathways related to cell cycle, cell communication and signal transduction. Individually, each of three miRNAs (miR-331, -98 and -33b) demonstrated significant correlation with the genes in cell cycle-related biological processes, which is consistent with important role of miRNAs in cell cycle regulation. Surprisingly, most miRNA-correlated genes were not direct targets predicted by mRNA target prediction program, TargetScan, suggesting indirect endogenous relationship between miRNAs and their correlated mRNAs. Conclusions/Significance: This study demonstrates feasibility of using naturally expressed transcript profiles to identify endogenous correlation between miRNA and miRNA. By applying this genome-wide approach, we have identified thousands of miRNA-correlated genes and revealed potential role of miRNAs in several important cellular functions. The study results along with accompanying data sets will provide a wealth of high-throughput data to further evaluate the miRNA-regulated genes and eventually in phenotypic variations of human populations.
Publication Title
Genome-wide transcriptional profiling reveals microRNA-correlated genes and biological processes in human lymphoblastoid cell lines.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina Genome Analyzer
Description
The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex (PRC2)-induced H3-K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin (Nnat) to decrease intracellular calcium (Ca2+) level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Functional complementation experiments with Nnat-3’UTR mutant, which is refractory to suppression by miR-708, rescued cell migration and metastasis defects. In breast cancer patients, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer. Overall design: Sequencing miRNAs from Human breast cancer cells: MCF10A, MCF7, MDA-MB-231, MDA-MB-LM2
Publication Title
Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples