Background: ETV6/RUNX1 (E/R) (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL) and also most likely the crucial factor for disease initiation, whereas its role in leukemia propagation and maintenance remains largely elusive. To address this issue we performed a shRNA-mediated knock-down (KD) of the E/R fusion gene and investigated the ensuing consequences on genome-wide gene expression patterns and deducible regulatory functions in two E/R-positive leukemic cell lines. Findings: Microarray analyses identified 777 genes whose expression was substantially altered. Although approximately equal proportions were either up- (KD-UP) or down-regulated (KD-DOWN), the effects on biological processes and pathways differed considerably. The E/R KD-DOWN set was significantly enriched for genes included in the cell activation, immune response, apoptosis, signal transduction and development and differentiation categories, whereas in the E/R KD-UP set only the PI3K/AKT/mTOR signaling and hematopoietic stem cells categories became evident. Comparable expression signatures obtained from primary E/R-positive ALL samples underline the relevance of these pathways and molecular functions. We also validated six differentially expressed genes representing the categories stem cell properties, B-cell differentiation, immune response, cell adhesion and DNA damage with RT-qPCR. Conclusion: The results of our analyses provide the first preliminary evidence that the continuous expression of the E/R fusion gene interferes with regular B-cell development by repressing key functions that are necessary under physiological circumstances. E/R may thus constitute also the essential driving force for the propagation and maintenance of the leukemic process irrespective of potential consequences of associated secondary changes. Finally, these findings may also provide a valuable source of potentially attractive therapeutic targets.
The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression.
Cell line, Treatment
View SamplesExposure to common environmental chemicals, including those found in personal care products has been linked to mammary cancer at high doses in animal models. Their effects at low doses at levels comparable to human exposure, especially during critical windows of development remain poorly understood. Using a Sprague-Dawley rat model, we investigated the effects of of three environmental chemicals diethyl phthalate (DEP), methyl paraben (MPB) and triclosan (TCS) on the transcriptome of normal developing mammary glands at low doses mimicking human exposure. Rats were exposed during three windows of early development perinatal (gestation day (GD) 1 - 20 or postnatal day (PND) 1 - 20), prepubertal (PND 21 - 41) and pubertal (PND 42 - 62), as well as chronic exposure from birth to end of lactation (PND 1 - 146). Mammary gland whole-transcriptomes were profiled by Affymetrix rat gene 2.0 st arrays.
Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development.
Sex, Specimen part
View SamplesThere is a lack of systematic investigations of large-scale transcriptome patterns associated with normal breast development. Herein, we profiled whole-transcriptome (by microarrays) of normal mammary glands in female Sprague-Dawley rats, an animal model widely used in breast cancer research, across six distinctive developmental stages pre-pubertal, peri-pubertal, pubertal, lactation, and adult parous and age-matched nulliparous.
Histology and Transcriptome Profiles of the Mammary Gland across Critical Windows of Development in Sprague Dawley Rats.
Sex, Specimen part
View SamplesGene expression data of glucocorticoid resistant and sensitive acute lymphoblastic leukemia cell lines for the article: Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells
Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells.
Specimen part, Treatment
View SamplesArticle title: Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells.
Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesGlucocorticoids (GC) have a major impact on the biology of normal and malignant cells of the lymphoid lineage. This includes induction of apoptosis which is exploited in the therapy of acute lymphoblastic leukemia (ALL) and related lymphoid malignancies. MicroRNAs (miRNAs) and the related mirtrons are ~22 nucleotide RNA molecules implicated in the control of essential biological functions including proliferation, differentiation and apoptosis. They derive from polymerase-II transcripts but whether GCs regulate miRNA-encoding transcription units is not known. We investigated miRNA/mirtron expression and GC regulation in 8 ALL in vitro models and 13 ALL children undergoing systemic GC monotherapy using a combination of expression profiling techniques, real time RT-PCR and northern blotting to detect mature miRNAs and/or their precursors. We identified a number of GC-regulated miRNAs/mirtrons, including the myeloid-specific miR-223 and the apoptosis and cell cycle arrest-inducing mir15~16 cluster. Thus, the observed complex changes in miRNA/mirtron expression during GC treatment might contribute to the anti-leukemic GC effects in a cell context dependent manner.
Glucocorticoid-regulated microRNAs and mirtrons in acute lymphoblastic leukemia.
No sample metadata fields
View SamplesTranscriptional microarray analysis was conducted on gastrocnemius muscle of control and PGC-1(i)skm-/- mice one week after the last tamoxifen administration using the Affymetrix Mouse Gene 1.0 ST.
The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defence in skeletal muscles.
Specimen part
View SamplesNotch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sex, Age, Specimen part, Treatment, Time
View SamplesPotassium is one of the essential macronutrients required for plant growth and development. It plays a major role in different physiological processes like cell elongation, stomatal movement, turgor regulation, osmotic adjustment, and signal transduction by acting as a major osmolyte and component of the ionic environment in the cytosol and subcellular organelles.
Gene expression analysis of rice seedling under potassium deprivation reveals major changes in metabolism and signaling components.
Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Knockout of G protein β5 impairs brain development and causes multiple neurologic abnormalities in mice.
Specimen part
View Samples