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GSE19675
Mus musculus
22 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent genetic studies in mice have established a key role for the nuclear receptor coregulator Trim24 in liver tumor suppression and provided evidence that Trim24 suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor alpha (Rara)-dependent transcription and cell proliferation. However, it is unknown which downstream targets of Rara regulated by Trim24 are critical for tumorigenesis. We report here that loss of Trim24 results in the overexpression of interferon (IFN)/STAT pathway genes in the liver, a process that occurs early in tumorigenesis and is more pronounced in tumors, despite the enhanced expression, late in the disease, of negative regulators such as Usp18, Socs1 and Socs2.
Publication Title
Tripartite motif 24 (Trim24/Tif1α) tumor suppressor protein is a novel negative regulator of interferon (IFN)/signal transducers and activators of transcription (STAT) signaling pathway acting through retinoic acid receptor α (Rarα) inhibition.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of KLS cells purified from bone marrow of mice conditionally inactivated for TIF1 gene. TIF1 deletion results in multiple defects in adult hematopoiesis. Results provide insight into the role of TIF1 in hematopoietic stem cells functions.
Publication Title
Adult hematopoiesis is regulated by TIF1γ, a repressor of TAL1 and PU.1 transcriptional activity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
TRIM24 and TRIM33 interact to form a corepressor complex that suppresses murine hepatocellular carcinoma (HCC). TRIM24 and TRIM33 cooperatively repress retinoic acid receptor dependent activity of VL30 retro-transposons in hepatocytes in vivo. In TRIM24 knockout hepatocytes, VL30 long terminal repeats (LTRs) generate enhancer (e)RNAs and act as surrogate promoter and enhancer elements deregulating expression of neighbouring genes. We show that a VL30 LTR-derived eRNA is essential to activate the lipocalin 13 gene in hepatocytes in vivo. A further consequence of VL30 de-repression is the accumulation of retro-transcribed VL30 DNA in the cytoplasm of TRIM24-mutant hepatocytes and activation of the viral defence/interferon response. VL30 activation therefore modulates gene expression via the enhancer activity of the LTRs and by activation of the interferon response. Both of these processes are genetically linked to HCC development suggesting that VL30 repression by TRIM24 plays an important role in tumour suppression. Overall design: RNA profiles in liver of wild type (WT) and Trim24-/- mice by deep sequencing using Illumina GAIIx.
Publication Title
Trim24-repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Primary effusion lymphoma is an aggressive B-cell lymphoma most commonly diagnosed in HIV-positive patients and universally associated with Kaposis sarcoma-associated herpesvirus (KSHV). Chemotherapy treatment of PEL yields only short-term remissions in the vast majority of patients yet efforts to develop superior therapeutic approaches have been impeded by lack of animal models that more accurately mimic human disease. To address this issue we developed a direct xenograft model, UM-PEL-1, by transferring freshly-isolated human PEL cells into the peritoneal cavities of NOD/SCID mice without in vitro cell growth. We utilized this model to show that bortezomib induces PEL remission and extends overall survival of mice bearing lymphomatous effusions. Transcriptome analysis by genomic arrays revealed that bortezomib downregulated cell cycle progression, DNA replication, and Myc-target genes.
Publication Title
Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Plasmablastic lymphoma is a high grade B cell lymphoma with plasmablastic morphology and a terminally differentiated B cell immunophenotype, usually arising in the setting of immunodeficiency and often demonstrating Epstein Barr Virus positivity. The molecular and genetic mechanisms underlying the pathogenesis of PBL are largely unknown. To better understand its pathogenesis, herein we have analyzed global gene expression of PBL and compared that to gene expression profiles of diffuse large B cell lymphoma. While overlaps in transcriptomes between these malignancies were identified, we have shown that the gene expression profile of plasmablastic lymphoma is distinct, demonstrating striking downregulation of B cell receptor signaling genes, BCL6, BCL11A SPI-B, targets of NFKB1, and upregulation of mitochondrial genes, PRMT5, MYC and MYC targets and IL21, implicating these alterations in the pathogenesis of this lymphoma. In addition we show the usefulness of SWAP-70 immunohistochemistry in the differentiation of immunoblastic diffuse large B cell lymphoma and plasmablastic lymphoma. Our findings provide justification for considering plasmablastic lymphoma as a specific lymphoma entity and provide insight into the unique transcriptional aberrations occurring in this high-grade lymphoma.
Publication Title
Gene expression analysis of plasmablastic lymphoma identifies downregulation of B-cell receptor signaling and additional unique transcriptional programs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcriptional coregulator Trim24 (formerly known as TIF1a) functions in mice as a liver-specific tumor suppressor. Mice carrying a null mutation in the Trim24 gene all develop hepatocellular carcinoma (HCC).
Publication Title
Loss of Trim24 (Tif1alpha) gene function confers oncogenic activity to retinoic acid receptor alpha.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
LMO2 regulates gene expression facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the Germinal Center (GC) reaction and is expressed in GC-derived non-Hodgkins lymphomas. LMO2 is one of the most powerful prognostic indicators in DLBCL patients. However, its function in GC B cells and DLBCL is currently unknown. In the present study we characterized the LMO2 transcriptome and interactome in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners such as LDB1, E2A, HEB, Lyl1, ETO2 and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, NFATc1 and LEF-1 proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF-1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provide a platform for future elucidation of LMO2 function in GC B-cells and DLBCL pathogenesis.
Publication Title
Identification of LMO2 transcriptome and interactome in diffuse large B-cell lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 63 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 over-expression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current therapies. Cyclin-D1 has been postulated as an effective therapeutic target, but its evaluation has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model whereby cyclin-D1 expression can be externally regulated. These mice developed lymphomas capable of recapitulating most features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo. However, using a combination of in vitro and in vivo assays, we identified a novel pro-survival cyclin-D1 function in MCL cells. Specifically, we demonstrate that cyclin-D1 sequestrates the pro-apoptotic protein BAX, thereby favoring BCL2 anti-apoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a pro-apoptotic BH3 mimetic synergistically killed murine lymphomas and human MCL cells. Our study identifies a novel role of cyclin-D1 in deregulating apoptosis and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL.
Publication Title
A cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression data from CD22+B220+ FACS-purified splenocytes of adult Sca1-HGAL knock-in CBAxC57BL/6J mice or wild-type littermates.
Publication Title
Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.
Sample Metadata Fields
Specimen part
View Samples