p65-/-Ras cells show delayed tumor formation in SCID mice. However, after prolonged latency, tumor formation was observed from these mice. To understand the changes of NF-kB regulated genes before and after tumor formation, RNA from p65+/+Ras, p65+/+RasTumor, p65-/-Ras, p65-/-RasTumor cells were isolated and microarray were performed.
NF-κB functions in tumor initiation by suppressing the surveillance of both innate and adaptive immune cells.
Specimen part
View SamplesNeurofibromatosis Type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating effects of hyperactive Ras in NF1 tumors are unknown. Cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs identified global negative feedback of genes that regulate Ras-Raf- MEK- extracellular signal-regulated protein kinase (ERK) signaling in both species. Nonetheless, activation of ERK was sustained in mouse and human neurofibromas and MPNST. PD0325901, a highly selective pharmacological inhibitor of MEK, was used to test whether sustained Ras-Raf-MEK-ERK signaling contributes to neurofibroma growth in the Nf1fl/fl;Dhh-cre mouse model or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in >80% of mice tested. PD0325901 also caused effects on tumor vasculature. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide strong rationale for testing MEK inhibitors in NF1 clinical trials.
MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors.
Specimen part
View SamplesUsing two independently derived murine BXH2 cell lines, Ara-C resistant derivatives were developed by exposure to increasing concentrations of Ara-C. Microarray analysis comparing the Ara-C resistant cells to their Ara-C sensitive parental cell lines identified potential genes involved in Ara-C resistance.
Deoxycytidine kinase is downregulated in Ara-C-resistant acute myeloid leukemia murine cell lines.
Specimen part, Cell line
View SamplesThis experiment was designed to identify transcripts that exhibit changes in abundance in the context of retinal degeneration by comparing transcript levels in adult wild type and prCAD -/- mouse retinas.
The genomic response to retinal disease and injury: evidence for endothelin signaling from photoreceptors to glia.
No sample metadata fields
View SamplesTranscriptional profiles were compared between dark adapted and light damaged BALBc (albino) mouse retinas.
The genomic response to retinal disease and injury: evidence for endothelin signaling from photoreceptors to glia.
No sample metadata fields
View SamplesFz4 and Fz8 cooperate in regulating the branching morhpogenesis of the developing kidney during mouse embryonic development, hence determines the eventual kidney size.
Genetic mosaic analysis reveals a major role for frizzled 4 and frizzled 8 in controlling ureteric growth in the developing kidney.
Specimen part
View SamplesSV40 large T antigen (TAg) contributes to cell transformation, in part, by targeting two well characterized tumor suppressors, pRb and p53. TAg expression affects the transcriptional circuits controlled by Rb and by p53. We have performed a microarray analysis to examine the global change in gene expression induced by wild-type TAg and TAg-mutants, in an effort to link changes in gene expression to specific transforming functions. For this analysis we have used enterocytes from the mouse small intestine expressing TAg. Expression of TAg in the mouse intestine results in hyperplasia and dysplasia. Our analysis indicates that practically all gene expression regulated by TAg in enterocytes is dependent upon its binding and inactivation of the Rb-family proteins.
Simian virus 40 T-antigen-mediated gene regulation in enterocytes is controlled primarily by the Rb-E2F pathway.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
NRASG12V oncogene facilitates self-renewal in a murine model of acute myelogenous leukemia.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sirt1 Regulates DNA Methylation and Differentiation Potential of Embryonic Stem Cells by Antagonizing Dnmt3l.
No sample metadata fields
View SamplesStem-cells and transformed cancer cells specifically express a polycomb repressive complex subtype, PRC4 which characteristically contains Sirt1 (Sirtuin-1), a NAD+ dependent class III histone deacetylase (HDAC) and Eed2 isoform as specific members. Analyzing the transcriptiome and methylome analysis of Sirt1 deficient murine ESCs (Sirt1-/- ESC), we demonstrate that these cells repressed specifically on some genomic imprinted and germ-line related genes.
Sirt1 Regulates DNA Methylation and Differentiation Potential of Embryonic Stem Cells by Antagonizing Dnmt3l.
No sample metadata fields
View Samples