Colony 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 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 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 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 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.
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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
View SamplesIn advanced malignancies, cancer cells have acquired capabilities to resist a variety of stress-inducing insults. We show that c-Jun N-terminal kinase (JNK) stress signaling is highly active in cancer cells from patients with late stage breast cancer and promotes tumor growth and metastasis in mouse models. Transcriptomic analysis revealed that JNK activity induces genes associated with extracellular matrix (ECM), wound healing and mammary stem cells. The ECM proteins and niche components osteopontin (SPP1) and tenascin C (TNC) are induced by JNK signaling and promote metastatic colonization of the lungs. Notably, treatment with chemotherapeutic drugs induces JNK activity in breast cancer cells, reinforcing the production of SPP1 and TNC. Inhibition of JNK or reduction of SPP1 or TNC expression sensitizes primary tumors and metastases in mice to chemotherapy.
Stress signaling in breast cancer cells induces matrix components that promote chemoresistant metastasis.
Specimen part, Cell line, Treatment
View SamplesPremature progesterone (P) rise during GnRH antagonist cycles for IVF is a frequent phenomenon and has been associated with lower pregnancy and implantation rates. Different thresholds of progesterone have been used so far to define its premature rise during the follicular phase of an IVF stimulated cycle. In this study, we evaluated endometrial gene expression on the day of oocyte retrieval according to the level of serum progesterone on the day of hCG administration in GnRH antagonist cycles.Endometrial biopsies from eleven patients were taken with a Pipelle de Cornier (Prodimed, Neuilly-en-Thelle, France) on the day of oocyte retrieval in a GnRH antagonist/rec-FSH stimulated IVF cycle with fresh embryo transfer. Biopsies were analysed for gene expression with Affymetrix Human Genome (HG) U133 Plus 2.0 Arrays and GCOS software (Affymetrix, Santa Clara, CA, USA). Patients were divided into three different groups according to their progesterone serum concentration on the day of hCG administration (A) P <= 0.9 ng/mL, (B) 1 < P < 1.5 ng/mL, and (C) P > 1.5 ng/mL. Serum P was measured with the automated Elecsys immunoanalyser (Roche Diagnostics, Mannheim, Germany). Selected differentially expressed genes were validated with quantitative real-time PCR (QPCR) with TaqMan Gene Expression Assays (Applied Biosystems, Foster City, CA, USA).
Progesterone rise on HCG day in GnRH antagonist/rFSH stimulated cycles affects endometrial gene expression.
Specimen part
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