We analyzed gene expression profiles of myeloma cells belonging to the group of bas prognosis RPMI 8226 and LP1 expressing either the GFP protein or a cyclin D1-GFP fusion protein
Cyclin D1 sensitizes myeloma cells to endoplasmic reticulum stress-mediated apoptosis by activating the unfolded protein response pathway.
Specimen part, Cell line
View SamplesEpidermal stem cells ensure proper faring of skin homeostatic processes under both physiological and challenging conditions. Currently, the molecular events underpinning ageing within the epidermal stem cell niche are poorly understood.
In Silico Analysis of the Age-Dependent Evolution of the Transcriptome of Mouse Skin Stem Cells.
Age, Specimen part
View SamplesWe have used microarray technology to identify the transcriptional targets of Rho subfamily GTPases. This analysis indicated that murine fibroblasts transformed by these proteins show similar transcriptomal profiles. Functional annotation of the regulated genes indicate that Rho subfamily GTPases target a wide spectrum of biological functions, although loci encoding proteins linked to proliferation and DNA synthesis/transcription are up-regulated preferentially. Rho proteins promote four main networks of interacting proteins nucleated around E2F, c-Jun, c-Myc, and p53. Of those, E2F, c-Jun and c-Myc are essential for the maintenance of cell transformation. Inhibition of Rock, one of the main Rho GTPase targets, leads to small changes in the transcriptome of Rho-transformed cells. Rock inhibition decreases c-myc gene expression without affecting the E2F and c-Jun pathways. Loss-of-function studies demonstrate that c-Myc is important for the blockage of cell-contact inhibition rather than for promoting the proliferation of Rho-transformed cells. However, c-Myc overexpression does not bypass the inhibition of cell transformation induced by Rock blockage, indicating that c-Myc is essential, but not sufficient, for Rock-dependent transformation. These results reveal the complexity of the genetic program orchestrated by the Rho subfamily and pinpoint protein networks that mediate different aspects of the malignant phenotype of Rho-transformed cells
Transcriptomal profiling of the cellular transformation induced by Rho subfamily GTPases.
No sample metadata fields
View SamplesThe guanosine triphosphatases of the Rho and Rac subfamilies regulate protumorigenic pathways and are activated by guanine nucleotide exchange factors (Rho GEFs), which could be potential targets for anticancer therapies. We report that two Rho GEFs, Vav2 and Vav3, play synergistic roles in breast cancer by sustaining tumor growth, neoangiogenesis, and many of the steps involved in lung-specific metastasis. The involvement of Vav proteins in these processes did not correlate with Rac1 and RhoA activity or cell migration, implying the presence of additional biological programs. Microarray analyses revealed that Vav2 and Vav3 controlled a vast transcriptional program in breast cancer cells through mechanisms that were shared between the two proteins, isoform-specific or synergistic. Furthermore, the abundance of Vav regulated transcripts was modulated by Rac1-dependent and Rac1-independent pathways. This transcriptome encoded therapeutically targetable proteins that played non redundant roles in primary tumorigenesis and lung-specific metastasis, such as integrin-linked kinase (Ilk), the transforming growth factorb family ligand inhibin bA, cyclooxygenase-2, and the epithelial cell adhesion molecule Tacstd2. It also contained gene signatures that predicted disease outcome in breast cancer patients. These results identify possible targets for treating breast cancer and lung metastases and provide a potential diagnostic tool for clinical use.
The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells.
Cell line
View SamplesWe used microarrays to investigate gene expression changes induced by the inhibition of RRAS2 expression using shRNA techniques to stably knockdown the endogenous transcripts of this GTPase in human MDA-MB-231-Luc cells.
Contribution of the R-Ras2 GTP-binding protein to primary breast tumorigenesis and late-stage metastatic disease.
Cell line
View SamplesCutaneous squamous tumors rely on autocrine/paracrine loops for proper fitness. Targeting this Achilles heel is therefore considered a potential avenue for patient treatment. However, the mechanisms that engage and sustain such programs during tumor ontogeny are poorly understood. Here, we show that two Rho/Rac activators, the exchange factors Vav2 and Vav3, control the expression of an epithelial autocrine/paracrine program that regulates keratinocyte survival and proliferation as well as the creation of an inflammatory microenvironment. Vav proteins are also critically involved in some of the subsequent autocrine signaling loops activated in keratinocytes. The genetic inactivation of both Vav proteins reduces tumor multiplicity without hampering skin homeostasis, thus suggesting that pan-specific Vav therapies may be useful in skin tumor prevention and treatment.
The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.
Specimen part
View SamplesRobles-Valero et al. report a tumor suppression role for the otherwise oncogenic Vav1 Rho GEF. This paradoxical action is mediated by the catalysis-independent buffering of Notch1 signaling in immature T cells.
A Paradoxical Tumor-Suppressor Role for the Rac1 Exchange Factor Vav1 in T Cell Acute Lymphoblastic Leukemia.
Specimen part, Treatment
View SamplesThe study used two Drosophila melanogaster fly lines, Alstonville and Dahomey, which have mitochondrial DNA variants but otherwise similar genomes. Female third instar larvae from both lines were fed on two diets, one with a 1:2 protein:carbohydrate ratio and the other with a 1:16 ratio. RNA was extracted and profiled by RNA-seq. Samples were sequenced on an Illumina Hiseq 2000 sequencer at the Ramaciotti Centre for Genomics, Sydney, Australia to produce 100bp paired end reads. At least 80 million read pairs were generated per sample. Overall design: Four independent replicates were obtained for each mitotype-diet combination.
Genotype to phenotype: Diet-by-mitochondrial DNA haplotype interactions drive metabolic flexibility and organismal fitness.
Subject
View SamplesWe aimed to identify specific biomarkers of IFN-beta bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFN-beta. Nine genes followed patterns in gene expression over time similar to the MX1 and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments revealed specific induction of selected biomarkers by IFN-beta but not IFN-gamma, and several markers, in particular USP18 and HERC5, were significantly induced at lower IFN-beta concentrations and more selective than the MX1 as biomarkers of IFN-beta bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p=0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFN-beta bioactivity, and to further explore their implication in MS pathogenesis.
Search for specific biomarkers of IFNβ bioactivity in patients with multiple sclerosis.
Sex, Age, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesAbstract: Drought is the primary cause of global agricultural losses and represents a major threat to worldwide food security. Currently, plant biotechnology stands out as the most promising strategy to increase crop growth in rain-fed conditions. The main mechanisms underlying drought resistance have been uncovered by studies of plant physiology and by engineering crops with drought-resistant genes. However, plants with enhanced drought resistance usually display lower levels of growth, highlighting the need to search for novel strategies capable of uncoupling drought resistance from growth. Here, we show that the brassinosteroid family of receptors, in addition to promoting growth, guides phenotypic adaptation to a great variety of drought stress traits analyzed herein. Whilst mutations in the ubiquitously localized BRI1 receptor pathway show an enhanced drought resistance at the expense of plant growth, we found that vascular-enriched BRL3 receptors confer drought tolerance without penalizing overall growth. Systematic analyses reveal that upon drought stress the BRL3 receptor pathway triggers the synthesis and mobilization of osmoprotectant metabolites, mainly proline and sugars. This preferentially occurs in the vascular tissues of the roots and favors overall plant growth. Altogether, our results uncover a new role for the spatial control of BR signaling in drought tolerance, and offer a novel strategy to address food security issues in an increasingly water-limited climate. Overall design: 28 days old root system were collected from soil, quickly washed in water and flash-frozen. Experiment with a bifactorial design. Factor one is the genotype, which include WT (Col-0) and 35S:BRL3. Factor two is the condition, which include control (Properly watered) and 5 days of drought (water-hold) conditions. 3 Biological replicates were collected per each genotype and condition.
Overexpression of the vascular brassinosteroid receptor BRL3 confers drought resistance without penalizing plant growth.
Specimen part, Subject
View Samples