Gene expression profiling of Hodgkin Lymphoma cell line following REL-B depletion
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Brian Lewis
PROVIDER: E-GEOD-35224 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:'The REL gene, encoding the NF-κB subunit c-Rel, is frequently amplified in B-cell lymphoma and functions as a tumour promoting transcription factor. Here we report the surprising result that c-rel -/- mice display significantly earlier lymphomagenesis in the c-Myc driven, Eμ-Myc model of B-cell lymphoma. c-Rel loss also led to earlier onset of disease in a separate TCL1-Tg driven lymphoma model. Tumour reimplantation experiments indicated that this is an effect intrinsic to the Eμ-Myc lymphoma cells but, counter-intuitively, c-rel -/- Eμ-Myc lymphoma cells were more sensitive to apoptotic stimuli. To learn more about why loss of c-Rel led to earlier onset of disease, microarray gene expression analysis was performed on B-cells from 4-week old, wild type and c-rel -/- Eμ-Myc mice. Extensive changes in gene expression were not seen at this age but among those transcripts significantly downregulated by the loss of c-Rel was the B-cell tumour suppressor BTB and CNC homology 2 (Bach2). Q-PCR and western blot analysis confirmed loss of Bach2 in c-Rel mutant Eμ-Myc tumours at both 4 weeks and the terminal stages of disease. Moreover Bach2 expression was also downregulated in c-rel -/- TCL1-Tg mice and RelA Thr505Ala mutant Eμ-Myc mice. Analysis of wild type Eμ-Myc mice demonstrated that the population expressing low levels of Bach2 exhibited the earlier onset of lymphoma seen in c-rel-/- mice. Confirming the relevance of these findings to human disease, analysis of ChIP-Seq data revealed that Bach2 is a c-Rel and NF-κB target gene in transformed human B-cells, while treatment of Burkitt''s lymphoma cells with inhibitors of the NF-κB/IKK pathway or deletion of c-Rel or RelA resulted in loss of Bach2 expression. This data reveals a surprising tumour suppressor role for c-Rel in lymphoma development explained by regulation of Bach2 expression, underlining the context dependent complexity of NF-κB signalling in cancer.'
2014-12-31 | E-MTAB-2774 | biostudies-arrayexpress
Project description:The expression array data will be merged with Rel-B ChIP-Seq data in HL cell lines. This will show REL-B direct and indirect controlled downstream target genes
2012-01-20 | GSE35224 | GEO
Project description:Bone marrow-derived macrophages were generated from bone marrow of naive WT or Rel-/- mice. After red blood cell lysis, BM cells were cultured in L929-conditioned medium for 7 days. After lipopolysaccharide (100 ng/mL) stimulation, RNAs were collected for microarray.
2020-03-10 | E-MTAB-8714 | biostudies-arrayexpress
Project description:c-Rel and RelA are members of the NF-kappaB family of transcription factors. They both have important roles in T cell activation. To discover where in the genome c-Rel and RelA bind and hence which genes they may directly target, we used ChIP-chip with EL4 cells stimulated with phorbol ester (PMA) and Ionomycin. We have identified regions in EL4 cells (background strain: C57BL/6N) activated for 2h or 8h by PMA and Ionomycin, that bind the transcription factors c-Rel and RelA. Immunoprecipitated samples from EL4 cells stimulated with PMA and ionomycin for 2 h and 8 h with antibodies against RelA or c-Rel respectively were used for ChIP-on-chip experiments. In addition, samples from total input and mock immunoprecipitation were used as controls. Biological triplicates were used.
2013-12-29 | E-GEOD-42818 | biostudies-arrayexpress
Project description:The ATR-CHK1 signalling pathway responds to single strand DNA breaks and is required for cancer cells to survive the high levels of DNA replication stress and genomic instability resulting from the activity of oncogenes such as MYC. For this reason, inhibitors of CHK1 have great potential as anti-cancer drugs and are currently in clinical trials. However, overcoming de novo or acquired resistance to CHK1 inhibition is required if these are to be used as effective therapies. We discovered that lymphomas from the E-Myc mouse model of MYC driven B-cell lymphoma, with a deletion of the c-Rel NF-B subunit, have defective CHK1 activity and are resistant to treatment with the highly specific CHK1i CCT244747. Here we use quantitative (phospho)proteomics approaches to investigate how de novo resistance to CHK1i is acquired and can be overcome, offering potential therapeutic opportunity in patients developing resistance to Chk1i in the clinic.
2022-10-19 | PXD026203 | Pride
Project description:Rel and RelA proteins were stably expressed in the chicken DT40 pre-B cell line and analyzed by transcription profiling to identify transformation-impacting genes regulated by NF-kB’s oncogenic v-Rel and c-Rel proteins. This analysis uncovered both common and differential gene expression profiles in cells expressing Rel vs. RelA proteins, and revealed that Rel protein expression can lead to gene-specific transcriptional repression, as seen for key B-cell receptor (BCR) components and signaling molecules like B-cell linker (BLNK), the B-cell adaptor for PI3K (BCAP) and Igλ. These were also downregulated in cells expressing a transformation-competent chimeric RelA/v-Rel protein, suggesting a correlation with the capacity of Rel proteins to transform lymphocytes. DNA binding, ChIP and transformation assays indicate that downregulation of BLNK and BCAP is an important contributing factor to the malignant transformation of lymphocytes by Rel and suggest that gene repression may be as important as transcriptional activation for the transforming activity of Rel proteins. Keywords: Comparative transcriptional profiling
2008-02-14 | GSE9544 | GEO
Project description:To further understand the role of c-Rel in fibrogensis, label-free mass spectrometric analysis was performed on the secretome of cultured WT and Rel-/- M0, M1 and M2 polarised macrophages as well as control and TGFB1-stimulated hepatocytes.
2020-09-28 | PXD017320 | Pride
Project description:Adaptive immunity and the five vertebrate NF-kB/Rel family members first appeared in cartilaginous fish, suggesting that NF-kB family expansion allowed the acquisition of new functions to regulate adaptive immune responses. Transcriptome profiling revealed that, even in macrophages, the NF-kB family member, c-Rel, most potently regulates a cytokine gene linked to adaptive immunity, Il12b, with limiting roles at key regulators of innate immunity. Neofunctionalization of c-Rel to regulate Il12b depends on its unique DNA-binding properties, which we examined using structural, biochemical, functional, and genomic approaches. Among our findings was functional c-Rel homodimer binding to motifs with little resemblance to canonical NF-kB motifs. To determine whether c-Rel’s unique binding properties drove c-Rel-RelA divergence, we compared binding properties in various vertebrate species. c-Rel-RelA binding properties diverged in mammals and amphibians but were comparable in earlier vertebrates, suggesting that divergent DNA binding emerged relatively late during vertebrate evolution to support increasing complexity of adaptive immune regulation.
2023-11-29 | GSE243010 | GEO
Project description:Adaptive immunity and the five vertebrate NF-kB/Rel family members first appeared in cartilaginous fish, suggesting that NF-kB family expansion allowed the acquisition of new functions to regulate adaptive immune responses. Transcriptome profiling revealed that, even in macrophages, the NF-kB family member, c-Rel, most potently regulates a cytokine gene linked to adaptive immunity, Il12b, with limiting roles at key regulators of innate immunity. Neofunctionalization of c-Rel to regulate Il12b depends on its unique DNA-binding properties, which we examined using structural, biochemical, functional, and genomic approaches. Among our findings was functional c-Rel homodimer binding to motifs with little resemblance to canonical NF-kB motifs. To determine whether c-Rel’s unique binding properties drove c-Rel-RelA divergence, we compared binding properties in various vertebrate species. c-Rel-RelA binding properties diverged in mammals and amphibians but were comparable in earlier vertebrates, suggesting that divergent DNA binding emerged relatively late during vertebrate evolution to support increasing complexity of adaptive immune regulation.
2024-03-11 | GSE243011 | GEO
Project description:Gallus gallus breed:REL Genome sequencing
| PRJNA392939 | ENA