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SRP076990
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
Half of prostate cancers are caused by a gene-fusion that enables androgens to drive expression of the normally silent ETS transcription factor ERG in luminal prostate cells1-4. Recent prostate cancer genomic landscape studies5-10 have reported rare but recurrent point mutations in the ETS repressor ERF11. Here we show these ERF mutations cause decreased protein stability and ERF mutant tumours are mostly exclusive from those with ERG fusions. ERF loss recapitulates the morphologic and phenotypic features of ERG gain in primary mouse prostate tissue, including expansion of the androgen receptor (AR) transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of PTEN loss that yields oncogenic activity by ERG. Furthermore, in a human prostate cancer model of ERG gain and wild-type ERF, ChIP-seq studies indicate that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites. Consistent with a competition model, ERF loss rescues ERG-positive prostate cancer cells from ERG dependency. Collectively, these data provide evidence that the oncogenicity of ERG is mediated, in part, by displacement of ERF and raise the larger question of whether other gain-of-function oncogenic transcription factors might also inactivate endogenous tumour suppressors. Overall design: Murine Pten+/+ prostates were infected with shNT or shErf lentivirus, selected with antibiotics and 2 rounds of FACS. For each condition, 2 sets of equal numbers of cells were plated and then processed for RNA extraction and RNA-seq independently.
Publication Title
ERF mutations reveal a balance of ETS factors controlling prostate oncogenesis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Glomerular podocyte cells are critical for the function of the renal ultrafiltration barrier. The highly specialized cell-cell junction of podocytes, the slit diaphragm, has a central role in the filtration barrier. Dendrin is a poorly characterized cytosolic component of the slit diaphragm in where it interacts with nephrin and Cd2ap. In this study, we have generated a dendrin knockout mouse line and explored the molecular interactions of dendrin. Dendrin-deficient mice were viable, fertile and had normal life span.
Publication Title
Wtip- and gadd45a-interacting protein dendrin is not crucial for the development or maintenance of the glomerular filtration barrier.
Sample Metadata Fields
Age, Specimen part
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Malignant catarrhal fever of cattle is associated with low abundance of IL-2 transcript and a predominantly latent profile of ovine herpesvirus 2 gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
We hypothesized that the relative abundances of host cell transcripts in lymph nodes of animals with malignant catarrhal fever (MCF), compared to healthy controls, may be used to identify pathways that may help to explain the pathogenesis of MCF. Therefore, an abundance of host cell gene expression patterns in lymph nodes of animals with MCF and healthy controls were analyzed by microarray. Indeed, a vast number of genes related to inflammatory processes, lymphocyte activation, cell proliferation and apoptosis were detected at different abundances. However, the IL-2 transcript was eminent among the transcripts, which were, compared to healthy controls, less abundant in animals with MCF. Compared to healthy cattle, bovines with MCF appear to mimic an IL-2 knockout phenotype that has been described in mice. This supports the hypothesis that immunopathogenic events are linked to the pathogenesis of MCF. IL-2-deficiency may play an important role in the process.
Publication Title
Malignant catarrhal fever of cattle is associated with low abundance of IL-2 transcript and a predominantly latent profile of ovine herpesvirus 2 gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
The goal of this study is to determine gene expression changes in the adult zebrafish spinal cord at 2 weeks after complete transection. Overall design: 2 samples were analyzed in duplicates: sham injured spinal cord and transected spinal cord at 2 weeks post-injury
Publication Title
Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of muscle mass occurs in a variety of diseases including cancer, chronic heart failure, AIDS, diabetes and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover recent results confirm that other TGF members control muscle mass. Using genetic tools we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF and induce an atrophy program which is MuRF1 independent and requires FoxO activity. Furthermore Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mTOR signalling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation especially when they are combined with IGF1-Akt activators.
Publication Title
Smad2 and 3 transcription factors control muscle mass in adulthood.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Microarray analysis of dithranol-treated psoriasis lesions before, during and after therapy
Publication Title
Dithranol targets keratinocytes, their crosstalk with neutrophils and inhibits the IL-36 inflammatory loop in psoriasis.
Sample Metadata Fields
Time
View Samples- Pseudomonas aeruginosa
- 3 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Pseudomonas aeruginosa PAO1 Two-Component Regulator CarSR Regulates Calcium Homeostasis and Calcium-Induced Virulence Factor Production through Its Regulatory Targets CarO and CarP.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 3 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
PAO1 was cultured planktonically to stationary phase with 10 mM calcium and no added calcium. The transcriptional response to calcium addition was determined.
Publication Title
The Pseudomonas aeruginosa PAO1 Two-Component Regulator CarSR Regulates Calcium Homeostasis and Calcium-Induced Virulence Factor Production through Its Regulatory Targets CarO and CarP.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In multiple myeloma (MM), hypoxia-inducible transcription factor-1 (HIF-1) is overexpressed in the MM cells of the hypoxic bone marrow (BM) microenvironment. Herein, we explored in MM cells the in vitro and in vivo effects of persistent HIF-1 inhibition by expression of a lentivirus shRNA pool on proliferation, survival and transcriptional and pro-angiogenic profiles. Among the significantly modulated genes (326 and 361 genes in hypoxic and normoxic condition, respectively), we found that HIF-1 inhibition in the human myeloma cell line JJN3 downregulates the pro-angiogenic molecules VEGF, IL8, IL10, CCL2, CCL5, and MMP9. Interestingly, several pro-osteoclastogenic cytokines were also inhibited, such as IL-7 and CCL3/MIP-1. The effect of HIF-1 inhibition was assessed in vivo in NOD/SCID mice both in subcutaneous and intratibial models, indicating in either case a dramatic reduction of weight and volume of the tumor burden as a consequence of HIF-1 knockdown. Moreover, a significant reduction of the number of vessels per field and VEGF immunostaining were observed. Finally, in the intra-tibial experiments, HIF-1 inhibition significantly blocks JJN3-induced bone destruction. Overall, our data indicate that HIF-1 suppression in MM cells significantly blocks MM-induced angiogenesis and reduces both tumor burden and bone destruction in vivo, strongly indicating HIF-1 as an emerging therapeutic target in MM.
Publication Title
Hypoxia-inducible factor (HIF)-1α suppression in myeloma cells blocks tumoral growth in vivo inhibiting angiogenesis and bone destruction.
Sample Metadata Fields
Specimen part, Cell line
View Samples