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GSE45748
Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Addiction of t(8;21) and inv(16) acute myeloid leukemia to native RUNX1.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cancer cells maintain a sensitive balance between growth-promoting oncogenes and apoptosis inhibitors. We show that WT RUNX1 is required for survival of t(8;21)-Kasumi-1 and inv(16)-ME-1 AML cell lines. The malignant AML phenotype is sustained by a delicate AML1-ETO/RUNX1 balance that involves competition for common DNA binding sites regulating a subset of AML1-ETO/RUNX1 targets.
Publication Title
Addiction of t(8;21) and inv(16) acute myeloid leukemia to native RUNX1.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
RUNX3 is one of three mammalian Runt-domain transcription factors that regulate gene expression in several types of immune cells. Runx3-deficiency in mice is associated with a multitude of defects in the adaptive and innate immunity systems, including the development of early onset colitis. Our study reveals that conditional deletion of Runx3 specifically in mononuclear phagocytes (MNP) recapitulates the early onset spontaneous colitis seen in Runx3-/- mice. We show that Runx3 is expressed in colonic MNP, including RM and the dendritic cell cDC2 subsets and its loss results in impaired differentiation/maturation of both cell types.
Publication Title
Runx3 prevents spontaneous colitis by directing the differentiation of anti-inflammatory mononuclear phagocytes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mouse models of hepatocellular carcinoma (HCC) simulate specific subgroups of human HCC. We investigated hepatocarcinogenesis in Mdr2-KO mice, a model of inflammation-associated HCC, using gene expression profiling and immunohistochemical analyses. Gene expression profiling demonstrated that although Mdr2-KO mice differ from other published murine HCC models, they share several important deregulated pathways and many coordinately differentially expressed genes with human HCC datasets. Analysis of genome positions of differentially expressed genes in liver tumors revealed a prolonged region of down-regulated genes on murine chromosome 8 in three of the six analyzed tumor samples. This region is syntenic to human chromosomal regions that are frequently deleted in human HCC and harbor multiple tumor suppressor genes. Real-time RT-PCR analysis of 16 tumor samples confirmed down-regulation of several tumor suppressors in most tumors. We demonstrate that in the aged Mdr2-KO mice, cyclin D1 nuclear level is increased in dysplastic hepatocytes that do not form nodules; however, it is decreased in dysplastic nodules and in liver tumors. We found that this decrease is mostly at the protein, rather than the mRNA level. These findings raise the question on the role of cyclin D1 at early stages of hepatocarcinogenesis in the Mdr2-KO HCC model. Furthermore, we show that most liver tumors in Mdr2-KO mice were characterized by the absence of b-catenin activation. In conclusion, the Mdr2-KO mouse may serve as a model for b-catenin-negative subgroup of human HCCs characterized by low nuclear cyclin D1 levels in tumor cells and by down-regulation of multiple tumor suppressor genes.
Publication Title
Molecular mechanisms of liver carcinogenesis in the mdr2-knockout mice.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The presence of the PUF (Pumilio/FBF) domain defines a conserved family of RNA-binding proteins involved in repressing gene expression. It has been suggested that a conserved function of PUF proteins is to repress differentiation and sustain the mitotic proliferation of stem cells. In humans, Pumilio2 (PUM2) is expressed in embryonic stem cells and adult germ cells.
Publication Title
PUMILIO-2 is involved in the positive regulation of cellular proliferation in human adipose-derived stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Specific genomic and transcriptomic aberrations in tumors induced by partial hepatectomy of a chronically inflamed murine liver.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Surgical resection is the preferred treatment for Hepatocellular carcinoma; however, it induces tumor recurrence. Our objective was to understand the molecular mechanisms linking liver regeneration under chronic-inflammation to tumorigenesis. Mdr2-knockout mice, a model of inflammation-associated cancer, underwent partial-hepatectomy which led to enhanced hepatocarcinogenesis. Yet, liver regeneration in these mice was severely attenuated. We demonstrate the activation of the DNA damage response machinery and altered genomic instability during early liver inflammatory stages resulting in hepatocyte apoptosis and cell-cycle arrest, and suggest their involvement in tumor recurrence subsequent to partial hepatectomy. We propose that under the regenerative proliferative stress induced by liver resection, the genomic unstable hepatocytes generated during chronic-inflammation, escape apoptosis and reenter the cell-cycle, triggering the enhanced tumorigenesis
Publication Title
Accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
We studied the molecular mechanisms of hepatocellular carcinoma (HCC) initiation and promotion using the Mdr2-knockout (Mdr2-KO) mice at pre-cancerous stages of liver disease. These mice lack the liver-specific P-glycoprotein responsible for phosphatidylcholine transport across the canalicular membrane. Portal inflammation ensues at an early age followed by the development of HCC between the ages of 12 and 15 months. Liver tissue samples of Mdr2-KO and control Mdr2-heterozygotes mice aged 3 and 12 months, were subjected to histological, biochemical and gene expression profiling analysis using Affymetrix Mouse Genome Array.
Publication Title
Multiple adaptive mechanisms to chronic liver disease revealed at early stages of liver carcinogenesis in the Mdr2-knockout mice.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background & Aims. Resection of hepatocellular carcinoma (HCC) tumors by partial hepatectomy (PHx) is associated with promoting hepatocarcinogenesis. We have previously reported that PHx promotes hepatocarcinogenesis in the Mdr2-knockout (Mdr2-KO) mouse, a model for inflammation-mediated HCC. Now, we explored the molecular mechanisms underlying the tumor-promoting effect of PHx in these mice. Methods. Using microarrays-based techniques, we compared genomic and transcriptomic profiles of HCC tumors developing in the Mdr2-KO mice either spontaneously or following PHx. Results. PHx accelerated HCC development in these mice by four months. PHx-induced tumors had only amplifications affecting multiple chromosomes and locating mainly near the acrocentric centromeres of murine chromosomes. Four different chromosomal regions were amplified each in at least three tumors. All tumors of untreated mice had chromosomal aberrations, including both deletions and amplifications. Comparison of gene expression profiles revealed a significantly enriched expression of oncogenes, chromosomal instability markers and E2F1 targets in the post-PHx compared to spontaneous tumors. Both tumor groups shared the same frequent amplification at chromosome 18. Here, we demonstrated that one of the regulatory genes encoded by this amplified region, Crem, was over-expressed in the nuclei of murine and human HCC cells in vivo, and that it stimulated proliferation of human HCC cells in vitro. Conclusions: PHx of a chronically inflamed liver directed tumor development to a discrete pathway characterized by amplification of specific chromosomal regions and expression of specific tumor-promoting genes. Crem is a new candidate HCC oncogene frequently amplified in this model and frequently over-expressed in human HCC.
Publication Title
Specific genomic and transcriptomic aberrations in tumors induced by partial hepatectomy of a chronically inflamed murine liver.
Sample Metadata Fields
Specimen part, Treatment
View Samples