Estrogen-related receptor (ERR) alpha is an orphan nuclear receptor highly expressed in the kidneys. ERRalpha is implicated in renal sodium and potassium homeostasis and blood pressure regulation. We used microarray analysis to identify differentially expressed genes in ERR alpha knockout mice kidneys versus wild-type. The results provide insight on the roles of ERRalpha in the kidney.
Physiological genomics identifies estrogen-related receptor alpha as a regulator of renal sodium and potassium homeostasis and the renin-angiotensin pathway.
Sex, Specimen part
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The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer.
Specimen part, Cell line
View SamplesTotal RNA was isolated from 3 WT and 3 ERRa null hearts and independent hybridizations were performed using MOE430 2.0 microarrays. Expression profiling was conducted to determine changes in gene expression in hearts lacking ERRa. The expression of genes involved in heart and muscle development, muscle contraction, lipid metabolism, OxPhos, protein metabolism and transcription were affected by the loss of ERRa.
Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma.
Sex, Specimen part
View SamplesReprogramming of cellular metabolism plays a central role in fuelling malignant transformation, and AMPK as well as the PGC-1/ERR axis are key regulators of this process. Intersection of gene expression and binding event datasets in breast cancer cells shows that activation of AMPK significantly increases the expression of PGC-1/ERR and promotes the binding of ERR to its cognate sites. Unexpectedly, the data also reveal that ERR, in concert with PGC-1, negatively regulates the expression of several one-carbon metabolism genes resulting in substantial perturbations in purine biosynthesis. This PGC-1/ERR-mediated repression of one-carbon metabolism promotes the sensitivity of breast cancer cells and tumors to the anti-folate drug methotrexate. These data implicate the PGC-1/ERR axis as a core regulatory node of folate cycle metabolism and further suggest that activators of AMPK could be used to modulate this pathway in cancer.
The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer.
Cell line
View Samples3 ventricles from E18.5 male mice were pooled for each array. Three arrays per genotype.
ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart.
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Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.
Cell line, Treatment
View SamplesWhether the nuclear fraction of mTOR plays a role in prostate cancer (PCa) and can participate in direct transcriptional crosstalk with the androgen receptor (AR) is as yet unknown. The intersection of gene expression, DNA binding-events, and metabolic studies uncovered the existence of a nuclear mTOR-AR transcriptional axis dictating the metabolic rewiring and nutrient usage of PCa cells. In human clinical specimens, nuclear localization of mTOR was significantly associated with metastasis and castration-resistant PCa (CRPC), correlating with a sustained metabolic gene program governed by mTOR in that context. This study thus uncovers an unexpected function of mTOR and underscores a paradigm shift from AR to mTOR as being the master transcriptional regulator of cell metabolism during PCa progression.
Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer.
Cell line
View SamplesERRa is an orphan nuclear receptor with an established role in cell metabolism. Our studies demonstrate that acute or chronic loss of ERRa broadly affects mitochondrial and glycolytic metabolism in CD4+ T cells and results in diminished T cell function and differentation.
Estrogen-related receptor-α is a metabolic regulator of effector T-cell activation and differentiation.
Specimen part, Treatment
View SamplesBACKGROUND: Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyse these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLA-matched RCC tumor cells.
miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction.
Sex, Age, Specimen part, Disease, Subject, Time
View SamplesAlbeit increased serum CK level and abnormal muscle histology are always present, boys with DMD are phenotipically indistinguishable from the normal ones at birth and, in their first years of life, acquire early motor milestones at normal times. A clear defect in muscle function becomes generally apparent by the end of the second year. As the disease is typically diagnosed between the ages of 3 and 7, the first two years are often considered and referred to as clinically presymptomatic.
Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.
Sex, Age
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