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GSE30428
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The right ventricle (RV) differs in several aspects from the left ventricle (LV) including its embryonic origin, physiological role and anatomical design. In contrast to LV hypertrophy, little is known about the molecular circuits, which are activated upon RV hypertrophy (RVH). We established a highly reproducible model of RVH in mice using pulmonary artery clipping (PAC), which avoids detrimental RV pressure overload and thus allows long-term survival of operated mice. Magnetic resonance imaging revealed pathognomonic changes with striking similarities to human congenital heart disease- or pulmonary arterial hypertension- patients. Comparative, microarray based transcriptome analysis of right- and left-ventricular remodeling identified distinct transcriptional responses to pressure-induced hypertrophy of either ventricle, which were mainly characterized by stronger transcriptional responses of the RV compared to the LV myocardium. Hierarchic cluster analysis revealed a RV- and LV-specific pattern of gene activity after induction of hypertrophy, however, we did not find evidence for qualitatively distinct regulatory pathways in RV compared to LV. Data mining of nearly three thousand RV-enriched genes under PAC disclosed novel potential (co)-regulators of long-term RV remodeling and hypertrophy. We reason that specific inhibitory mechanisms in RV restrict excessive myocardial hypertrophy and thereby contribute to its vulnerability to pressure overload.
Publication Title
Identification of right heart-enriched genes in a murine model of chronic outflow tract obstruction.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Uncontrolled Transforming growth factor-beta (TGF) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGF-mediated cues are directed to induce late-stage tumorigenic events is poorly understood, particularly given that TGF has clear tumor suppressing activity in other contexts. Here we demonstrate that the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of the Hippo pathway, are necessary to promote and maintain TGF-induced tumorigenic phenotypes in breast cancer cells. Interactions between TAZ/YAP, TGF-activated SMAD2/3, and TEAD transcription factors reveal convergent roles for these factors in the nucleus. Genome-wide expression analyses indicate that TAZ/YAP, TEADs and TGF-induced signals coordinate a specific pro-tumorigenic transcriptional program. Importantly, genes cooperatively regulated by TAZ/YAP, TEAD, and TGF, such as the novel targets NEGR1 and UCA1, are necessary for maintaining tumorigenic activity in metastatic breast cancer cells. Nuclear TAZ/YAP also cooperate with TGF signaling to promote phenotypic and transcriptional changes in non-tumorigenic cells to overcome TGF repressive effects. Our work thus identifies crosstalk between nuclear TAZ/YAP and TGF signaling in breast cancer cells, revealing novel insight into late-stage disease-driving mechanisms.
Publication Title
The transcriptional regulators TAZ and YAP direct transforming growth factor β-induced tumorigenic phenotypes in breast cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Our study identified long term salt stress treatment to induce symptoms similar to developmental senescence. In order to identify possible crosstalk components shared between developmental and salt-triggered senescence.
Publication Title
Salt stress and senescence: identification of cross-talk regulatory components.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Methylated DNA binding protein 2 (MBD2) has been shown to bind specific methylated promoters and suppress transcription. Here we systematically investigate MBD2 suppression by overexpressing MBD2 in MCF-10A cells and generating gene expression profiles of overexpressing cells and normal MCF-10A cells.
Publication Title
Methylated DNA binding domain protein 2 (MBD2) coordinately silences gene expression through activation of the microRNA hsa-mir-496 promoter in breast cancer cell line.
Sample Metadata Fields
Cell line, Treatment
View Samples- Schizosaccharomyces pombe
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Mitotic entry is accompanyed by the expression of a cluster of so called mitotic genes, whose activation is critical for mitosis in human and yeast cells. We found a link between the transcription machinery and cell cycle control network at mitosis in fission yeast, involving the Cdk8 kinase dependent phosphorylation of the fork head transcription factor Fkh2. We have generated a non-phosphorylatable fkh2 mutant (fkh2-S2A) also.
Publication Title
Cyclin-dependent kinase 8 regulates mitotic commitment in fission yeast.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Definition of the landscape of promoter DNA hypomethylation in liver cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Sex differences in rat adrenal cortex are manifested as larger adrenal volume of cortex and higher corticosterone secretion by females compared with males. The molecular bases of these sex related differences are poorly understood.
Publication Title
Transcriptome Profile of Rat Adrenal Evoked by Gonadectomy and Testosterone or Estradiol Replacement.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness.
Sample Metadata Fields
Sex, Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Extensive loss of DNA methylation is a hallmark of cancer. The role of hypomethylation in altering gene expression in cancer cells has been poorly understood. Hepatic cellular carcinoma (HCC) is one of the most common human cancers. We use HCC as a model to investigate hypomethylation in cancer by a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays. We identify approximately 2,800 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appear in clusters across the genome suggesting a high-level organization behind the epigenomic changes in cancer. The genes whose promoters are demethylated are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility and invasion; functions that are essential for cancer progression and metastasis. Previous studies suggested that MBD2 was involved in demethylation of uPA and MMP2 genes in human breast and prostate cancer cell lines. We extend these results here showing that whereas MBD2 depletion in normal liver cells has little or no effect, its depletion in the human hepatocellular carcinoma cell line HepG2 and the adenocarcinoma cell line SkHep1 results in suppression of cell growth, anchorage-independent growth and invasiveness, as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Our studies establish for the first time the rules governing hypomethylation of promoters in liver cancer and define the potential functional role of hypomethylation in cancer.
Publication Title
Definition of the landscape of promoter DNA hypomethylation in liver cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from noninvasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness.
Publication Title
A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness.
Sample Metadata Fields
Sex, Disease, Disease stage, Cell line
View Samples