Docetaxel is the standard first line therapy for hormone-refractory prostate cancer patients. Here we generated models of Docetaxel resistance in prostate cancer cells to study the molecular pathways that drive the acquisition of resistance to this therapy. We used microarrays to detail the global program of gene expression underlying the acquisition of Docetaxel resistance in prostate cancer cells.
Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells.
Specimen part, Cell line
View SamplesThe MaxiK potassium channel is a key modulator of smooth muscle tone. Due to its calcium and voltage sensitivity, MaxiK is activated following depolarization and Ca2+ mobilization, therefore relaxing the muscle. We investigate the effects of silencing MaxiK for 48h in corpus cavernosuml smooth muscle (CCSM) cells to identify possible mechanisms of compensation through molecular crosstalk between pathways regulating smooth muscle tone.
Silencing MaxiK activity in corporal smooth muscle cells initiates compensatory mechanisms to maintain calcium homeostasis.
Specimen part
View SamplesIn the present study, the transcriptional analysis of CD biopsies reveals profound alterations in the ileum transportome profile. More than 60 SLC transporters showed different expression pattern compared with the healthy donors, being mostly decreased. Changes were confirmed in almost all the eighteen altered SLCs analyzed by RT-PCR. The results obtained display alterations in amino acid transporters, purinome members, Zn transporters and metallothioneins. All together, these alterations which mainly involve transporters localized at the apical membrane of the enterocyte anticipate impaired amino acid uptake and purinergic responses. Remarkably, incubation of explants with specific commensal bacteria restored almost all CD transportome alterations.
Transportome Profiling Identifies Profound Alterations in Crohn's Disease Partially Restored by Commensal Bacteria.
Specimen part, Disease
View SamplesThe effects of mercury (HgCl2) on barley (Hordeum vulgare L.) growth, physiological traits and gene expression profiles were studied. The shoot to root ratio was decreased in the two levels of HgCl2 (500 and 1000 M) assayed, which was related primarily with decreases in shoot dry weight. Moreover stomatal conductance was limited and leaf carbon isotope discrimination decreased. Therefore water uptake limitations seem to be an important component of barley responses to HgCl2. Evidences for decreased stomatal conductance and water uptake limitations were further confirmed by the over expression of ABA related transcripts and down regulation of an aquaporin in roots. Root dry weight was only affected at 1000 M HgCl2 and root browning was observed, while several transcripts for lignin biosynthesis were up regulated in HgCl2. Microarray analysis further revealed that growth inhibition in HgCl2 was related to increased expression of genes participating in ethylene biosynthesis and down regulation of several genes participating in DNA synthesis, chromatin structure and cell division, cell wall degradation and modification, oxidative pentose phosphate cycle and nitrogen metabolism pathway. Genes involved in detoxification and defence mechanisms were up regulated including several cytochrome P450s, glucosyltransferases and glutathione-s-transferases and amino acid metabolism participatory genes. It is concluded that barley plants survive in the presence of HgCl2 through several mechanisms that include water uptake limitations, shoot and root growth regulation, increased expression of genes involved in the biosynthesis of several plant protection secondary metabolites and finally through detoxification.
Molecular and physiological mechanisms associated with root exposure to mercury in barley.
Specimen part
View SamplesUsing EWS-FLI and its parental transcription factor, FLI1, we created a unique experimental system to address questions regarding the genomic mechanisms by which chimeric transcription factors cause cancer. We found that in tumor cells, EWS-FLI targets regions of the genome distinct from FLI1, despite identical DNA-binding domains. In primary endothelial cells, however, EWS-FLI and FLI1 demonstrate similar targeting. To understand this mistargeting, we examined chromatin organization. Regions targeted by EWS-FLI are normally repressed and nucleosomal in primary endothelial cells. In tumor cells, however, bound regions are nucleosome-depleted and harbor the chromatin signature of enhancers. We next demonstrated that through chimerism, EWS-FLI acquired the ability to alter chromatin. Expression of EWS-FLI results in nucleosome depletion at targeted sites, whereas silencing of EWS-FLI in tumor cells restored nucleosome occupancy. Thus, the EWS-FLI chimera acquired chromatin-altering activity, leading to mistargeting, chromatin disruption, and ultimately transcriptional dysregulation.
Tumor-specific retargeting of an oncogenic transcription factor chimera results in dysregulation of chromatin and transcription.
Cell line
View SamplesThe transcription factor GATA2 regulates chemotherapy resistance in prostate cancer. We report a novel GATA2 transcriptional program that has implications for chemotherapy resistance disease and aggressiveness in castration resistant prostate cancer. Overall design: Examination of the transcriptional network changes induced in human Ch-CRPC cell lines by two shRNA mediated knock down of GATA2 versus random shRNA control
A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer.
No sample metadata fields
View SamplesWe report the transcriptional response of the zebrafish digestive organs to an acute high-fat feed using RNASeq analysis and highlight the changes in gene expression involved in the synthesis, storage, and dispersal of lipids. These key physiological responses to a high-fat meal all stem from the endoplasmic reticulum (ER), where lipids are formed and assigned to their fates. Overall design: A feeding time course was undertaken with 6.5-dpf larval zebrafish. Triplicate samples were independently prepared from pairwise crosses fed either high-fat or low-fat food. 5% egg yolk emulsion (high-fat) feeds and 10% egg white (low-fat) feeds were prepared. At the appropriate time points, digestive organs (intestine, liver, pancreas) were dissected from 10 anesthetized larval zebrafish. Unfed controls were used to determine a transcriptional baseline.
Endoplasmic Reticulum Lipid Flux Influences Enterocyte Nuclear Morphology and Lipid-dependent Transcriptional Responses.
No sample metadata fields
View SamplesFlowering time is a complex trait regulated by many genes that are integrated in different genetic pathways. Different genetic screenings carried out during the past decades have revealed an intrincated genetic regulatory network governing this trait. Efforts aimed at improving our understanding of how such genetic pathways respond to genetic and enviromental cues are needed.
The arabidopsis DNA polymerase δ has a role in the deposition of transcriptionally active epigenetic marks, development and flowering.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative genomic evidence for the involvement of schizophrenia risk genes in antipsychotic effects.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Combined chromatin and expression analysis reveals specific regulatory mechanisms within cytokine genes in the macrophage early immune response.
Cell line
View Samples