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GSE53394
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Cancer cell motility and invasiveness are fundamental characteristics of the malignant phenotype and are regulated through diverse signaling networks involving kinases and transcription factors. In this study, we identify a nuclear hormone receptor (ER)-protein kinase (ERK5)-cofilin (CFL1) network that specifies the degree of breast cancer cell aggressiveness through coupling of actin reorganization and hormone receptor-mediated transcription. Using dominant negative and constitutively active forms, as well as small molecule inhibitors of ERK5 and MEK5, we show that hormone activation of estrogen receptor- determines the nuclear versus cytoplasmic localization of the MAPK family member ERK5, which functions as a coregulator of ER-gene transcription.
Publication Title
Novel roles for ERK5 and cofilin as critical mediators linking ERα-driven transcription, actin reorganization, and invasiveness in breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The nuclear hormone receptor, estrogen receptor-alpha (ER), and MAP kinases both play key roles in hormone-dependent cancers, yet their interplay and the integration of their signaling inputs remain poorly understood. In these studies, we document that estrogen-occupied ER activates and interacts with ERK2, a downstream effector in the MAPK pathway, resulting in ERK2 and ER colocalization at chromatin binding sites across the genome of breast cancer cells.
Publication Title
Genomic collaboration of estrogen receptor alpha and extracellular signal-regulated kinase 2 in regulating gene and proliferation programs.
Sample Metadata Fields
Disease, Disease stage, Cell line, Time
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The transcription factor FOXM1 coordinates the expression of cell cycle-related genes and plays a pivotal role in tumorigenesis and cancer progression. We have previously shown that FOXM1 acts downstream of 14-3-3 signaling, which correlates with a more aggressive tumor phenotype. However, the role that FOXM1 might play in engendering the resistance to endocrine treatments in estrogen receptor-positive (ER+) patients when tumor FOXM1 is high, has not been clearly defined.
Publication Title
The forkhead transcription factor FOXM1 promotes endocrine resistance and invasiveness in estrogen receptor-positive breast cancer by expansion of stem-like cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The closely related transcription factors (TFs), estrogen receptors ER and ER, regulate divergent gene expression programs and proliferative outcomes in breast cancer. Utilizing MCF-7 breast cancer cells with ER, ER, or both receptors as a model system to define the basis of differing response specification by related TFs, we show that these TFs and their key coregulators, SRC3 and RIP140, generate overlapping as well as unique chromatin-binding and transcription-regulating modules.
Publication Title
Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 30 Downloadable Samples
IlluminaHiSeq2000
Description
The MCF-7 were infected with either control adenovirus expressing B-galactosidase (Ad) or adenovirus expressing ERB (AdERbeta) for 72 h. For knockdown of the endogenous ERa in MCF-7 cells, cells were treated with siRNA for 24h (AdERbeta+SiERalpha). Then cells were treated with Veh (0.1% EtOH), 10 nM E2 or 1 uM BEs (botanical extracts) for 24h. Overall design: Duplicate samples run; treatment after knockdown included a control treatment (V), estradiol (E2) or botanical extracts; genistein (Gen), S-equol, liquiritigenin (Liq)
Publication Title
Transcriptomic analysis identifies gene networks regulated by estrogen receptor α (ERα) and ERβ that control distinct effects of different botanical estrogens.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2000
Description
There is great medical need for estrogens having favorable pharmacological profiles, supporting desirable activities for menopausal women such as metabolic and vascular protection but lacking stimulatory activities on the breast or uterus. Here, we report the development of structurally novel estrogens with favorable target tissue-selective estrogenic activity. Through a process of structural alteration of the hormone estradiol that preserves essential chemical and physical features of estradiol but greatly moderates its binding affinity for the estrogen receptors (ERs), we obtained Pathway Preferential Estrogens (PaPEs) capable of having interaction with ER that is sufficient to activate the extranuclear-initiated signaling pathway preferentially over the direct nuclear-initiated pathway. PaPE modulate a pattern of gene regulation and cellular and biological processes that result in essentially no stimulation of reproductive and mammary tissues and breast cancer cells, but have a favorable pattern of activity on metabolic tissues and the vasculature. The structural permutation process represents a novel approach to govern the balance in utilization of extranuclear vs. nuclear pathways of ER action to obtain tissue-selective/non-nuclear pathway-preferential estrogens, which should prove to be beneficial for postmenopausal hormone replacement. The approach may also have broad applicability for other members of the nuclear hormone receptor superfamily. Overall design: 24 samples; inhibitor and time course experiments
Publication Title
Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
The goal of this study is to compare gene expression levels in uhrf1 mutants with global DNA hypomethylation to WT siblings Overall design: 10 whole embryos were pooled per sample of either 5 dpf old uhrf1 mutants or phenotypically WT siblings and RNA was extracted. Libraries were prepared according to Illumina Truseq RNA sample prep kit, version 2, followed by Ribo-Zero Gold treatment
Publication Title
Loss of DNA methylation in zebrafish embryos activates retrotransposons to trigger antiviral signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.
Publication Title
Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Androgen receptor (AR) is the major therapeutic target in aggressive prostate cancer. However, targeting AR alone can result in drug resistance and disease recurrence. Therefore, simultaneous targeting of multiple pathways could in principle be an effective new approach to treating prostate cancer. Here we provide proof-of-concept that a small molecule inhibitor of nuclear ß-catenin activity (called C3) can inhibit both the AR and ß-catenin signaling pathways that are often misregulated in prostate cancer. Treatment with C3 ablated prostate cancer cell growth by disruption of both ß-catenin/TCF and ß-catenin/AR protein interaction, reflecting the fact that TCF and AR have overlapping binding sites on ß-catenin. Given that AR interacts with, and is transcriptionally regulated by ß-catenin, C3 treatment also resulted in decreased occupancy of ß-catenin on the AR promoter and diminished AR and AR/ß-catenin target gene expression. Interestingly, C3 treatment resulted in decreased AR binding to target genes accompanied by decreased recruitment of an AR and ß-catenin cofactor, CARM1, providing new insight into the unrecognized function of ß-catenin in prostate cancer. Importantly, C3 inhibited tumor growth in an in vivo xenograft model, and blocked renewal of bicalutamide-resistant sphere forming cells, indicating the therapeutic potential of this approach. Overall design: Compare and contrast the expression profile of prostate cancer cells treated with a Wnt inhibitor (C3) with respect to ß-catenin and AR knockdown (all samples in duplicates).
Publication Title
Inhibition of androgen receptor and β-catenin activity in prostate cancer.
Sample Metadata Fields
Disease, Subject
View Samples