KRAS mutations are the ost abundand driver mutations found in lung adenocarcinoma patients. Unfortunately, there are no clinical approved inhibitors available, to directly target mutant forms of KRAS. The aim of the study was to unravel the impact of upstream Egfr activation in signaling of mutated K-ras. We found that upregulation of G12D mutant Kras induced genes was significantly impaired when Egfr was knocked out. Our data suggests that signaling of mutant Kras depends on upstream activation. This finding may be exploited therapeutically by targeting EGFR in KRAS mutant patients. Overall design: We isolated mouse alveolar type II cells and induced the Kras G12D mutation, with and without concomitant Egfr knockout, in vitro. Cells lysates were analyzed 5 days following transgene induction.
JAK-STAT inhibition impairs K-RAS-driven lung adenocarcinoma progression.
Specimen part, Cell line, Subject
View SamplesPostnatal neural progenitors of the enteric nervous system are a potential source for future cell replacement therapies of developmental dysplasia like Hirschsprung's disease. However, little is known about the molecular mechanisms driving the homeostasis and differentiation of this cell pool. In this work, we conducted Affymetrix gene chip experiments to identify differences in gene regulation between proliferation and early differentiation of enteric neural progenitors. We detected a total of 1333 regulated genes that were linked to different groups of cellular mechanisms involved in cell cycle, apoptosis, neural proliferation, and differentiation. As expected, we found a strong inhibition of cell cycle progression as well as an enhanced expression of neuronal and glial markers. We further found a marked inactivation of the canonical Wnt pathway during the beginning of cellular differentiation. Taken together, this data illustrated the various mechanisms taking place during the proliferation and early differentiation of enteric neural progenitor cells.
Comparative Microarray Analysis of Proliferating and Differentiating Murine ENS Progenitor Cells.
Specimen part
View SamplesGenome-wide profiling establishes that human cytomegalovirus (HCMV) exerts an extensive, unforeseen level of specific control over which cellular mRNAs are recruited to or excluded from polyribosomes.
Global reprogramming of the cellular translational landscape facilitates cytomegalovirus replication.
Specimen part, Disease, Treatment
View SamplesThe Hippo pathway is an emerging signaling cascade involved in the regulation of organ size control. It consists of evolutionally conserved protein kinases that are sequentially phosphorylated and activated. The active Hippo pathway subsequently phosphorylates a transcription coactivator, YAP, which precludes its nuclear localization and transcriptional activation. Identification of transcriptional targets of YAP in diverse cellular contexts is therefore critical to the understanding of the molecular mechanisms in which the Hippo pathway restricts tissue growth.
Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer.
Specimen part
View SamplesHow type I / II interferons (IFNs) prevent periodic re-emergence of latent pathogens in tissues of diverse cell-types remains unknown. Using homogenous neuron cultures latently-infected with herpes simplex virus (HSV), we show that extrinsic type I or II IFN act directly on neurons to induce unique gene expression signatures and inhibit the reactivation-specific burst of viral genome-wide transcription called Phase I. Surprisingly, IFNs suppressed reactivation only during a limited period early in Phase I preceding productive virus growth. Sensitivity to type II IFN was selectively lost if viral ICP0, which normally accumulates later in Phase I, was expressed prior to reactivation. Thus, IFNs suppress reactivation by preventing initial expression of latent genomes but are ineffective once Phase I viral proteins accumulate and limit IFN action. This demonstrates that inducible reactivation from latency is only transiently sensitive to IFNs. Moreover, it illustrates how latent pathogens escape host immune control to periodically replicate by rapidly deploying an interferon-resistant state. Overall design: Superior cervical ganglia (SCG) neuron cultures harboring reactivating HSV-1 treated with IFNb or IFNg. Neurons were harvested for RNA 20h after reactivation (in the presence or absence of IFN) for RNA-seq. Libraries were generated following Illumina Truseq Ribo-Zero protocol.
Immune Escape via a Transient Gene Expression Program Enables Productive Replication of a Latent Pathogen.
No sample metadata fields
View SamplesDifferentiation assays with neural progenitor cells of the enteric nervous system (ENS) showed elongated neurite outgrowth under influence of 3,5,3'-Triiodothyronine (concentrations 50 nm and 100 nm). For analysis, neural cells were stained with TUJ1 (beta-Tubulin III). Microarray analysis should enlighten these results on a genetical basis and give hints about the regulation pathways.
Molecular and cell biological effects of 3,5,3'-triiodothyronine on progenitor cells of the enteric nervous system in vitro.
Specimen part, Treatment
View SamplesHere we harnessed the potential of RNA sequencing in 89 human pancreatic islet donors to identify genes and exons regulated in this relevant tissue for T2D. Overall design: mRNA profiles of 89 human pancreatic islet donors having different levels of blood glucose (HbA1c) with and without T2D. The data was generated by deep sequencing using Illumina HiSeq 2000.
Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction.
Sex, Age, Specimen part, Subject
View SamplesThese patients proved resistant to docetaxel treatment, exhibiting residual tumor of 25% or greater remaining volume.
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.
No sample metadata fields
View SamplesThese patients were sensitive to docetaxel treatment, exhibiting less than 25% residual tumor.
Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.
No sample metadata fields
View Samplesneuroblastoma cells derived from PDOX models were treated with the kinase inhibitor. Overall design: 5 repetitions of control and IBL-302 treated cells were harvest and submitted for RNAseq analysis
Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.
Specimen part, Treatment, Subject
View Samples