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GSE71109
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Selective RAF inhibitors including vemurafenib (PLX4032) have demonstrated clinical efficacy in mutant BRAF driven metastatic melanoma. The clinical effectiveness of RAF inhibitors depends on near complete abolition of the MAPK pathway output in tumors harboring BRAF mutations. However these compounds paradoxically activate the MAPK pathway in cells bearing oncogenic RAS or elevated upstream receptor signaling. This paradox can promote cellular proliferation and can manifest clinically with progression of secondary malignancies such as cutaneous squamous cell carcinomas (cuSCC). We have identified next generation RAF inhibitors (paradox breakers, e.g. PLX7904) that inhibit mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation.
Publication Title
RAF inhibitors that evade paradoxical MAPK pathway activation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is over-expressed in CLL and is enriched proximal to genes up-regulated or de novo expressed in CLL with known function in disease pathogenesis and progression. These genes, including key members of the BCR signaling pathway, provide rationale for this therapeutic approach to identify new targets in alternative types of cancer. Additionally, we describe PLX51107, a structurally distinct BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in pre-clinical models of CLL. Herein, the discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.
Publication Title
BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 78 Downloadable Samples
NextSeq 500
Description
Slow-cycling subpopulations exist in bacteria, yeast, and mammalian systems. In the case of cancer, slow-cycling subpopulations have been proposed to give rise to drug resistance. However, the origin of slow-cycling human cells is poorly studied, in large part due to lack of markers to identify these rare cells. Slow-cycling cells pass through a non-cycling period marked by low CDK2 activity and high p21 levels. Here, we use this knowledge to isolate these naturally slow-cycling cells from a heterogeneous population and perform RNA-sequencing to delineate the transcriptome underlying the slow-cycling state. We show that cellular stress responses – the p53 transcriptional response and the integrated stress response – are the most salient causes of spontaneous entry into the slow-cycling state. Overall design: mRNA profiling of spontaneously quiescent human cells and cells forced into quiescence by four different methods
Publication Title
Spontaneously slow-cycling subpopulations of human cells originate from activation of stress-response pathways.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Laser capture microdissection coupled with microarray genes expression analysis were utilized in order to elucidate the regulatory networks active in epithelial cells of the neonatal and adult mouse uterus.
Publication Title
Cell-specific transcriptional profiling reveals candidate mechanisms regulating development and function of uterine epithelia in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify genes differentially expressed in the glandless uterus, whole uteri were collected from control (uterine glands present) and PUGKO (no uterine glands) mice at day of pseudopregnancy (DOPP) 3.5 (day DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the glandless uteri of PUGKO mice as compared to control mice.
Publication Title
Cell-specific transcriptional profiling reveals candidate mechanisms regulating development and function of uterine epithelia in mice.
Sample Metadata Fields
Specimen part
View Samples- Escherichia coli
- 3 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Transcriptional analysis of the effects of the deletion of the sRNAs glmY and glmZ in EHEC
Publication Title
Global analysis of posttranscriptional regulation by GlmY and GlmZ in enterohemorrhagic Escherichia coli O157:H7.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 120 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis has been established as a tool for the characterization of genotoxic mechanisms of chemical mutagens. This approach has been shown to differentiate between DNA reactive genotoxins and non-DNA reactive or indirectly-acting genotoxins. In this context, it has been suggested that expression analysis is capable of distinguishing compounds that cause DNA damage from those that interfere with mitotic spindle function. Formaldehyde (FA) is known to be a DNA-reactive substance which mainly induces chromosomal damage in cultured mammalian cells. However, there has been concern that FA might also act as an aneugen (i.e., induce aneuploidy) but recent cytogenetic studies did not support this assumption. To further characterize FA's genotoxic mode of action, we now used gene expression profiling as a molecular tool to differentiate between clastogenic and aneugenic activity. TK6 cells were exposed to FA for 4 and 24 h and changes in gene expression were analyzed using a whole-genome human microarray. Results were compared to the expression profiles of two DNA-damaging clastogens (methyl methanesulfonate [MMS] and ethyl methanesulfonate [EMS]) and two aneugens (colcemid [COL] and vincristine [VCR]). The gene expression profiles indicated that clastogens and aneugens induce discriminable gene expression patterns. The expression profile of FA showed more similarities to clastogens than to aneugens. Hierarchical clustering analysis as well as several class prediction algorithms revealed a much closer relationship of FA with clastogens than with aneugens. A pathway analysis of differentially regulated genes also demonstrated an overall better agreement of FA with clastogens than with aneugens. Altogether, the results of this study revealed great similarities in gene expression in response to FA and clastogens but did not support an aneugenic activity of FA.
Publication Title
Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using various exposure conditions, we studied the induction of DNA-protein crosslinks (DPX) by formaldehyde (FA) and their removal in primary human nasal epithelial cells (HNEC). DPX were indirectly measured by the alkaline comet assay as the reduction of gamma ray induced DNA migration. DPX are the most relevant primary DNA alterations induced by FA and the comet assay is a very sensitive method for the detection of FA-induced DPX. In parallel experiments, we investigated changes in gene expression by using a full genome human microarray. After a single treatment with FA (50 to 200 M), concentration and time-dependent changes in gene expression were seen under conditions that also induced genotoxicity. Repeated treatments with low FA concentrations (20 and 50 M) did not lead to a significant induction of DPX but repeated treatments with 50 M FA changed the expression of more than 100 genes. Interestingly, the expression of genes involved in the main pathway for FA detoxification and the repair of DPX were not specifically enhanced. A high degree of overlap was seen among the pattern of gene changes induced by FA in HNEC in comparison to recently published array studies for nasal epithelial cells from rats exposed to FA in vivo. Our results suggest that HNEC are a suited in vitro model for the characterization of FA-induced toxicity and the relationship between genotoxic and other cytotoxic effects.
Publication Title
Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify candidate genes regulated by forkhead transcription factor box A2 (FOXA2) in the uterus, control and Foxa2-deleted uteri were collected at day of pseudopregnancy (DOPP) 3.5 (DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the Foxa2-deleted as compared to control uteri that are candidiate FOXA2-regulated genes in the uterus.
Publication Title
Integrated chromatin immunoprecipitation sequencing and microarray analysis identifies FOXA2 target genes in the glands of the mouse uterus.
Sample Metadata Fields
Specimen part
View Samples