This SuperSeries is composed of the SubSeries listed below.
Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators.
Specimen part, Cell line
View SamplesThe 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.
Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators.
Specimen part, Cell line
View SamplesWe used microarrays to detail the global transcriptional response mediated by ERalpha or ERbeta to the phytoestrogen genistein in the MCF-7 human breast cancer cell model.
Estrogen Receptors alpha and beta as determinants of gene expression: influence of ligand, dose, and chromatin binding.
No sample metadata fields
View SamplesThe 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)
Transcriptomic analysis identifies gene networks regulated by estrogen receptor α (ERα) and ERβ that control distinct effects of different botanical estrogens.
No sample metadata fields
View SamplesThere 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
Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues.
No sample metadata fields
View SamplesTo identify genes involved in TBI outcomes in Drosophila we compared genome-wide mRNA expression of uninjured and injured flies under both age and diet conditions. Overall design: Whole male fly mRNA profiles of 0-7 day and 20-27d old Drosophila line w1118 were generated, with or without injury and under two different dietary conditions. Experiments were preformed in triplicate, using Illumina HiSeq 2500.
Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila.
Sex, Specimen part, Subject
View SamplesNFX1-91, a novel E6 cellular downstream target, functions as a transcriptional regulator and is involved in repressing hTERT expression. Other functions and downstream targets regulated by NFX1-91 were not well understood. We used microarrays to determine gene expression deregulated when NFX1-91 was knocked down.
NFX1 plays a role in human papillomavirus type 16 E6 activation of NFkappaB activity.
Cell line
View SamplesGoal: To compare the gene expression profiles from pediatric patients with each other, with those reported in adults and in those related to exosomes.
Differential gene expression of soluble CD8+ T-cell mediated suppression of HIV replication in three older children.
Sex, Specimen part
View SamplesTwo subtypes of the estrogen receptor, ERalpha and ERbeta, mediate the actions of estrogens, and the majority of human breast tumors contain both ERalpha and ERbeta. To examine the possible interactions and modulatory effects of ERbeta on ERalpha activity, we have used adenoviral gene delivery to produce human breast cancer (MCF-7) cells expressing ERbeta, along with their endogenous ERalpha. We have examined the effects of ER expression on genome-wide gene expression by Affymetrix GeneChip microarrays. We find that ERbeta modulated estrogen gene expression on nearly 24% of E2-stimulated genes but only 8% of E2-inhibited genes. We find that ERbeta modulation is gene-specific, enhancing or counteracting ERalpha regulation for distinct subsets of estrogen target genes. Introduction of ERbeta into ERalpha-containing cells induced up/down-regulation of many estrogen target in the absence of any added ligand. In addition, ERbeta presence elicited the expression of a unique set of genes that were not regulated by ERalpha alone. ERbeta modulated the expression of genes in many functional categories, but the greatest numbers were associated with transcription factor and signal transduction pathways. Regulation of multiple components in the TGF beta, SDF1, and semaphorin pathways, may contribute to the suppression of proliferation observed with ERbeta both in the presence and absence of estrogen. Hence, ERbeta modulates ERalpha gene regulation in diverse ways that may contribute to its growth-inhibiting beneficial effects in breast cancer
Impact of estrogen receptor beta on gene networks regulated by estrogen receptor alpha in breast cancer cells.
No sample metadata fields
View SamplesCancer 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.
Novel roles for ERK5 and cofilin as critical mediators linking ERα-driven transcription, actin reorganization, and invasiveness in breast cancer.
Specimen part
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