Diagnostic samples of peripheral blood form acute myeloid leukemia were analysed for gene expression differences
NFATc1 as a therapeutic target in FLT3-ITD-positive AML.
Sex, Specimen part
View SamplesThe second messenger cAMP acts via protein kinase A (PKA) to induce apoptosis by mechanisms that are poorly understood. Here, we assessed a role for mitochondria and analyzed gene expression in cAMP/PKA-promoted apoptosis by comparing wild-type (WT) S49 lymphoma cells and the S49 variant, D- (cAMP-deathless), which lacks cAMP-promoted apoptosis but has wild-type levels of PKA activity and cAMP-promoted G1 growth arrest. Treatment of WT, but not D-, S49 cells with 8-CPT-cAMP for 24 h induced loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and Smac and increase in caspase-3 activity. Gene expression analysis (using Affymetrix 430 2.0 Arrays) revealed that WT and D- cells incubated with 8-CPT-cAMP have similar, but non-identical, extents of cAMP-regulated gene expression at 2h (~800 transcripts) and 6h (~1000 transcripts) (|Fold|>2, P<0.06); by contrast, at 24h ~2500 and ~1100 transcripts were changed in WT and D- cells, respectively. Using an approach that combined regression analysis, clustering and functional annotation to identify transcripts that showed differential expression between WT and D- cells, we found differences in cAMP-mediated regulation of mRNAs involved in transcriptional repression, apoptosis, the cell cycle, RNA splicing, Golgi and lysosomes. The 2 cell lines differed in CREB phosphorylation and expression of the transcriptional inhibitor Icer and in cAMP-regulated expression of genes in the Inhibitor of apoptosis (IAP) and Bcl families. The findings indicate that cAMP/PKA-promoted apoptosis of lymphoid cells occurs via mitochondrial-mediated events and imply that such apoptosis involves gene networks in multiple biochemical pathways.
Gene expression signatures of cAMP/protein kinase A (PKA)-promoted, mitochondrial-dependent apoptosis. Comparative analysis of wild-type and cAMP-deathless S49 lymphoma cells.
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View SamplesAbstract
Gene expression patterns define key transcriptional events in cell-cycle regulation by cAMP and protein kinase A.
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View SamplesBone marrow-derived dendritic cells from C57BL/6 mice were treated with 1 ug/ml cholera toxin, 10 uM forskolin or control medium for 2 h.
Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax.
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View SamplesCaspases, proteolytic enzymes involved in cell death could play a role independent of cell death in the developing heart
Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart.
Age, Specimen part
View SamplesColony Stimulating Factor 1(CSF1) is known to promote osteoclast progenitor survival but its role in regulating osteoclast differentiation and mature osteoclast function are less well understood.
The transcription factor T-box 3 regulates colony-stimulating factor 1-dependent Jun dimerization protein 2 expression and plays an important role in osteoclastogenesis.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Neuronopathic Gaucher disease: dysregulated mRNAs and miRNAs in brain pathogenesis and effects of pharmacologic chaperone treatment in a mouse model.
Specimen part
View SamplesIn GnRH-antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression
In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Stress signaling in breast cancer cells induces matrix components that promote chemoresistant metastasis.
Specimen part, Cell line, Treatment
View SamplesABSTRACT:Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by using islet tissue culture with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or transplanted in female recipients that became pregnant (day 12.5), male islets induced the islet pregnancy gene signature, which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in male and female beta cells.
Prolactin receptors and placental lactogen drive male mouse pancreatic islets to pregnancy-related mRNA changes.
Sex, Specimen part
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