Transcription profiling of mice Pax5 targets in B-macrophage bipotential lymphoma cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Andrei Thomas-Tikhonenko
PROVIDER: E-MEXP-1156 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2006-09-08 | E-MEXP-757 | biostudies-arrayexpress
Project description:This microarray experiment was designed to identify genes and pathways modulated in ovarian cancer xenografts treated with anti-human VEGF mAb (Bevacizumab). Tumors were established in NOD/SCID mice by s.c. injection of human ovarian cancer cells (IGROV-1 and SKOV3). Mice were treated with the anti-VEGF monoclonal antibody Bevacizumab or with PBS (control). Total RNA was extracted from tumor samples and hybridized on Affymetrix GeneChip™ PrimeView™ Human Gene Expression Arrays. Each sample was derived from a different mouse (n=5 mice/group). In order to evaluate the effects of the anti-human VEGF mAb in the two models, expression data of IGROV-1 and SKOV3 derived tumors were normalized and analyzed separately. Raw microarray data, preprocessed data matrix and results of differential expression analysis are available together with the applied protocols.
2019-12-16 | E-MTAB-7683 | biostudies-arrayexpress
Project description:Despite advances in contemporary chemotherapeutic strategies, long term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. In order to validate our oxaliplatin sensitivity signature, Patient-Derived Colorectal Cancer Explants (PDCCEs) were developed in NOD-SCID mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (Sensitivity=87.5%; Specificity=100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer. Fourty-two human tumors and murine explants of colorectal origin, both primary colon and of various metastatic sites, were processed for total RNA. The samples included RNA from 14 patient samples in addition to RNA from Patient-Derived Colorectal Cancer Explant (PDCCEs) generated from these 14 patient samples. The PDCCEs were processed as fresh frozen whole tumor in addition to formalin-fixed paraffin-embedded (FFPE) tumors.
2012-02-17 | E-GEOD-28691 | biostudies-arrayexpress
Project description:In lymphomas derived from mature B cells the expression of the transcription factor PAX5 is maintained whereas classical Hodgkin lymphoma displays significantly reduced PAX5 expression despite its derivation from mature B cells. To elucidate the functional role of PAX5 in classical Hodgkin lymphoma, we re-established the PAX5 expression in the Hodgkin cell line L428 with and without epigenetic modulation. To this end, we stably transfected the Hodgkin cell line L428 with an inducible PAX5 expression construct. Although the overexpressed PAX5 was transcriptionally active as demonstrated by synthetic reporter constructs, no induction of the B-cell phenotype was achieved. PAX5 chromatin immunoprecipitation with subsequent next generation sequencing in B-cell lines and the PAX5 overexpressing L428 cell line showed different binding patterns. Since epigenetic restrictions might affect PAX5 binding, combined DNA demethylation and histone acetylation was performed. However, no re-expression of B-cell genes was observed also under these conditions. Thus, PAX5 is not sufficient for the re-activation of the B-cell program in Hodgkin cells despite epigenetic opening of the chromatin. This clearly indicates that the repression of the B-cell identity of the Hodgkin cells is caused and secured by complex molecular mechanisms. 2 Burkitt lymphoma cell lines (Raji, Namalwa), the Hodgkin lymphoma cell line L428 and the PAX5-producing L428 (L428-PAX5) with or without 5-aza-2M-bM-^@M-2-deoxycytidine/Trichostatin A treatment were analysed in triplicate.
2013-07-30 | E-GEOD-44244 | biostudies-arrayexpress
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2017-05-19 | PXD005592 | Pride
Project description:In lymphomas derived from mature B cells the expression of the transcription factor PAX5 is maintained whereas classical Hodgkin lymphoma displays significantly reduced PAX5 expression despite its derivation from mature B cells. To elucidate the functional role of PAX5 in classical Hodgkin lymphoma, we re-established the PAX5 expression in the Hodgkin cell line L428 with and without epigenetic modulation. To this end, we stably transfected the Hodgkin cell line L428 with an inducible PAX5 expression construct. Although the overexpressed PAX5 was transcriptionally active as demonstrated by synthetic reporter constructs, no induction of the B-cell phenotype was achieved. PAX5 chromatin immunoprecipitation with subsequent next generation sequencing in B-cell lines and the PAX5 overexpressing L428 cell line showed different binding patterns. Since epigenetic restrictions might affect PAX5 binding, combined DNA demethylation and histone acetylation was performed. However, no re-expression of B-cell genes was observed also under these conditions. Thus, PAX5 is not sufficient for the re-activation of the B-cell program in Hodgkin cells despite epigenetic opening of the chromatin. This clearly indicates that the repression of the B-cell identity of the Hodgkin cells is caused and secured by complex molecular mechanisms. Analysis of genome-wide PAX5 binding sites in B-cell lines (Raji, Namalwa) and the PAX5-producing Hodgkin cell line L428-PAX5 by ChIP-Seq
2013-07-30 | E-GEOD-44551 | biostudies-arrayexpress
Project description:B lymphopoiesis is a key developmental event orchestrated by a complex combinatorial action of lineage-specific transcription factors. In early B cell progenitors, lineage commitment is directly mediated by the master regulator PAX5, whose deficiency is commonly associated with B cell Acute Lymphoblastic Leukemia (B-ALL). Despite its essential role in mammalian immunity, the regulatory mechanisms that control PAX5 function remain largely unknown. Here we show that NAD+-dependent enzyme SIRT7 coordinates B cell development progression through PAX5. We have identified a SIRT7-dependent regulatory switch based on dynamic deacetylation of a single PAX5 residue, which controls its activity and thereby B cell fate. While a PAX5K198 acetylated mimic is incapable of inducing both B cell development and identity due to reduced protein stability and impaired binding to chromatin, deacetylation of this residue boosts PAX5 activity, leading to massive gene repression and in vivo restoration of B cell commitment but not differentiation. These findings suggest an unexpected uncoupling of hematopoietic differentiation and lineage commitment. Further supporting the functional relevance of the SIRT7-PAX5 axis, the interplay between both factors is conserved in human B-ALL, where high SIRT7 expression is an independent good prognostic factor. Our findings unveil a crucial mechanism in the regulation of B cell production based on the control of PAX5 function and underscore the key role of Sirtuins in the regulation of the immune system.
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Project description:Purpose: Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct clinical behavior, resistance to androgen ablation, and frequent but short responses to chemotherapy. The model systems we report reflect the biology of the human disease and can be used to improve our understanding of SCPC and to develop new therapeutic strategies for it. Experimental Design: We developed a set of CRPC xenografts and examined their fidelity to their human tumors of origin. We compared the expression and genomic profiles of SCPC and large cell neuroendocrine carcinoma (LCNEC) xenografts to those of typical prostate adenocarcinoma xenografts and used a panel of 60 human tumors to validate our findings using immunohistochemistry. Results: We show that SCPC and LCNEC xenograft models retain high fidelity to their human tumors of origin and are characterized by a marked upregulation of UBE2C and other M-phase cell cycle genes in the absence of AR, retinoblastoma (RB1) and cyclin D1 (CCND1) expression and confirm these findings in a panel of CRPC patients’ samples. In addition, array comparative genomic hybridization of the xenografts showed that the SCPC/LCNEC tumors display more copy number variations than the adenocarcinoma counterparts and that there is amplification of the UBE2C locus and microdeletions of RB1 in a subset of these, but no AR nor CCND1 deletions. Moreover, the AR, RB1, and CCND1 promoters showed no CpG methylation in the SCPC xenografts. Conclusion: Modeling human prostate cancer with xenografts allows in-depth and detailed studies of its underlying biology. The detailed clinical annotation of the donor tumors enables associations of anticipated relevance to be made. Futures studies in the xenografts will address the functional significance of the findings. Total of 6 samples
2012-01-01 | E-GEOD-33053 | biostudies-arrayexpress
Project description:Pax5 controls B-cell commitment, development and immunity by repressing B-lineage-inappropriate genes and activating B-cell-specific genes. In addition to the N-terminal DNA-binding paired domain, Pax5 contains a conserved octapeptide, partial homeodomain and C-terminal sequences with transactivating and inhibitory potential. To understand how the C-terminal domains of Pax5 contribute to the repression and activation function of Pax5, we performed Pax5 pulldown combined with mass spectrometry to identify coactivator or corepressor complexes that bind to the C-terminal regions of Pax5.
2023-08-24 | PXD040424 | Pride
Project description:Purpose: Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct clinical behavior, resistance to androgen ablation, and frequent but short responses to chemotherapy. The model systems we report reflect the biology of the human disease and can be used to improve our understanding of SCPC and to develop new therapeutic strategies for it. Experimental Design: We developed a set of CRPC xenografts and examined their fidelity to their human tumors of origin. We compared the expression and genomic profiles of SCPC and large cell neuroendocrine carcinoma (LCNEC) xenografts to those of typical prostate adenocarcinoma xenografts and used a panel of 60 human tumors to validate our findings using immunohistochemistry. Results: We show that SCPC and LCNEC xenograft models retain high fidelity to their human tumors of origin and are characterized by a marked upregulation of UBE2C and other M-phase cell cycle genes in the absence of AR, retinoblastoma (RB1) and cyclin D1 (CCND1) expression and confirm these findings in a panel of CRPC patients’ samples. In addition, array comparative genomic hybridization of the xenografts showed that the SCPC/LCNEC tumors display more copy number variations than the adenocarcinoma counterparts and that there is amplification of the UBE2C locus and microdeletions of RB1 in a subset of these, but no AR nor CCND1 deletions. Moreover, the AR, RB1, and CCND1 promoters showed no CpG methylation in the SCPC xenografts. Conclusion: Modeling human prostate cancer with xenografts allows in-depth and detailed studies of its underlying biology. The detailed clinical annotation of the donor tumors enables associations of anticipated relevance to be made. Futures studies in the xenografts will address the functional significance of the findings. 22 samples were analysed, that included MDA PCa 79 (n = 3), 117-9 (n = 3), 130 (n = 2), 144-4 (n = 4), 144-13 (n = 5), 146-10 (n = 3), 155-2 (n = 1), and 155-12 (n = 1). MDA PCA 79, 117-9 and 130 samples had the pathologic characteristics of prostate adenocarcinoma and were compared against MDA PCA 144-4, 144-13, 146-10 and 155-12 that have the pathologic features of prostate small cell/ large cell neuroendocrine carcinoma
2012-01-01 | E-GEOD-32967 | biostudies-arrayexpress