Analysis of changes in gene expression levels after after prolonged exposure of triple-negative breast cancer cell lines to low doses of Panobinostat (LBH589), a pan-histone deacetylase inhibitor. Overall design: RNA-sequencing was performed after 96 hours and 4 weeks of incubation 10 nmol/L of LBH589 of two triple-negative breast cancer cell lines (HCC1806 and MDA-MB-231). All the expreiments were performed in biological triplicates
Genome-wide chromatin accessibility, DNA methylation and gene expression analysis of histone deacetylase inhibition in triple-negative breast cancer.
Cell line, Treatment, Subject
View SamplesWe performed a transcriptomic analysis of Pi starvation responses in Arabidopsis thaliana (Columbia-0) wild type plants under phosphate starvation stress and in plants with altered PHR1(-like) activity, comparing mutants of phr1 and phr1-phl1 grown in phosphate-lacking medium. Results show the central role of PHR1 and functionally redundant members of its family in the control of transcriptional responses to Pi starvation.
A central regulatory system largely controls transcriptional activation and repression responses to phosphate starvation in Arabidopsis.
Specimen part
View SamplesWe performed a transcriptomic analysis of Pi starvation responses in Arabidopsis thaliana (Columbia-0) phr1 mutant plants expressing PHR1 in presence of cicloheximide, that inhibit protein translation, thus preventing any effect of PHR1 on the expression of indirect targets. Results show the primary target genes of PHR1 in the responses to Pi starvation.
A central regulatory system largely controls transcriptional activation and repression responses to phosphate starvation in Arabidopsis.
No sample metadata fields
View SamplesWe performed a transcriptomic analysis of Pi-starvation and recovery after resupplying Pi in Arabidopsis thaliana (Columbia-0) wild type plants and double mutant spx1,spx2. Results show that SPX1 is a Pi-dependent inhibitor of the transcription factor PHR1, a central regulatory protein in the control of transcriptional responses to Pi starvation.
SPX1 is a phosphate-dependent inhibitor of Phosphate Starvation Response 1 in Arabidopsis.
Age, Specimen part
View SamplesMelanoma is a highly aggressive cancer with increasing incidence rates and a poor survival, particularly in patients with AJCC stage IV and advanced stage III. Deregulation of NF-kB is linked to different pathological states, including melanoma. To identify the involvement of NF-kB pathway regulation in melanoma progression, we manipulated NF-kB pathway activation and profiled gene expression using RNA-sequencing. Overall design: mRNA profiles of IM-0223 cells overexpressing KPC1 (KPC1) or control (V0) generated by deep sequencing using Illumina HiSeq 2500.
Epigenetic Regulation of KPC1 Ubiquitin Ligase Affects the NF-κB Pathway in Melanoma.
No sample metadata fields
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 Samples