Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA196906 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice. Profiling Smarcb1 dependent gene expression we find genes which are dependent on Smarcb1 expression to be enriched for ECM and cell adhesion functions. We identify Igfbp7, which is related to the insulin-like growth factor binding proteins family, as a downstream target of Smarcb1 transcriptional activity, and show that re-introduction of Igfbp7 alone can hinder tumor development. Two cancer cell lines, 167 and 365, derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice were re-infected with a retro-viral vector for Smarcb1 re-expression or an empty retro-viral vector as control. Total-RNA was collected 3 days post infection so as to enrich for direct targets of Smarcb1 transcriptionaly regulated genes
2013-12-31 | E-GEOD-46017 | biostudies-arrayexpress
Project description:SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice. Profiling Smarcb1 dependent gene expression we find genes which are dependent on Smarcb1 expression to be enriched for ECM and cell adhesion functions. We identify Igfbp7, which is related to the insulin-like growth factor binding proteins family, as a downstream target of Smarcb1 transcriptional activity, and show that re-introduction of Igfbp7 alone can hinder tumor development.
2013-12-31 | GSE46017 | GEO
Project description:To identify mutant p53 GOF, murine primary osteosarcomas expressing p53R172H or p53R245W over null and p53-null osteosarcomas were processed for bulk sequencing; DEGs were identified in p53R172H and p53R245W expressing tumors by comparing to p53-null tumors; DEGs were used to identify dysregulated pathways and mutant p53 GOF
2023-05-12 | GSE231849 | GEO
Project description:The claudin-low subtype is a recently identified rare molecular subtype of human breast cancer that expresses low levels of tight and adherens junction genes and shows high expression of epithelial-to-mesenchymal transition (EMT) genes. These tumors are enriched in gene expression signatures derived from human tumor initiating cells (TIC) and human mammary stem cells. Through cross-species analysis, we discovered mouse mammary tumors that have similar gene expression characteristics as human claudin-low tumors and were also enriched for the human TIC signature. Such claudin-low tumors were similarly rare, but came from a number of distinct mouse models including the p53 null transplant model. Here we present a molecular characterization of fifty p53 null mammary tumors as compared to other mouse models and human breast tumor subtypes. Similar to human tumors, the murine p53 null tumors fell into multiple molecular subtypes including two basal-like, a luminal, a claudin-low, and a subtype unique to this model. The claudin-low tumors also showed high gene expression of EMT inducers, low expression of the miR-200 family, and low to absent expression of both claudin 3 and E-cadherin. These murine subtypes also contained distinct genomic DNA copy number changes some of which are similarly altered in their cognate human subtype counterpart. Finally, limiting dilution transplantation revealed that p53 null claudin-low tumors are highly enriched for TICs as compared to the more common adenocarcinomas arising in the same model, thus providing a novel preclinical mouse model to investigate the therapeutic response of TICs. 107 Agilent CGH and expression microarrays
2011-08-14 | E-GEOD-27101 | biostudies-arrayexpress
Project description:SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex, is the causative gene of pediatric and juvenile cancers such as rhabdoid tumors and epithelioid sarcomas. Here, we used a dual siRNA screening method based on the “simultaneous inhibition of a paralog pair” concept to identify a paralog pair comprising acetyltransferases CBP and p300 as a synthetic lethal target in SMARCB1-deficient cancers. Treatment with CBP/p300 dual inhibitors suppressed growth of cell lines and tumor xenografts derived from SMARCB1-deficient cells but not SMARCB1-proficient cells. SMARCB1-containing SWI/SNF complexes localized with H3K27me3 (a marker of transcriptional repression) and its methyltransferase, EZH2, at the promotor region of the KREMEN2 locus. By contrast, SMARCB1 deficiency led to localization of H3K27ac (a marker of transcriptional promotion) and recruitment of its acetyltransferases CBP and p300 at the KREMEN2 locus, resulting in transcriptional upregulation of KREMEN2, which cooperates with the SMARCA1 chromatin remodeling complex instead of SMARCB1-deficient residual SWI/SNF complexes. Simultaneous inhibition of CBP/p300 led to transcriptional downregulation of KREMEN2 and then induced apoptosis by monomerization of KREMEN1 due to a failure to interact with KREMEN2, which suppressing anti-apoptotic signaling pathways. Taken together, our findings indicate that simultaneous inhibitors of CBP/p300 could be promising therapeutic agents for SMARCB1-deficient cancers.
2024-04-29 | GSE237043 | GEO
Project description:We used microarrays to compared gene re-expression of SMARCB1 in I2A SMARCB1-deficient rhabdoid tumor cell line.
2017-11-02 | GSE98277 | GEO
Project description:The claudin-low subtype is a recently identified rare molecular subtype of human breast cancer that expresses low levels of tight and adherens junction genes and shows high expression of epithelial-to-mesenchymal transition (EMT) genes. These tumors are enriched in gene expression signatures derived from human tumor initiating cells (TIC) and human mammary stem cells. Through cross-species analysis, we discovered mouse mammary tumors that have similar gene expression characteristics as human claudin-low tumors and were also enriched for the human TIC signature. Such claudin-low tumors were similarly rare, but came from a number of distinct mouse models including the p53 null transplant model. Here we present a molecular characterization of fifty p53 null mammary tumors as compared to other mouse models and human breast tumor subtypes. Similar to human tumors, the murine p53 null tumors fell into multiple molecular subtypes including two basal-like, a luminal, a claudin-low, and a subtype unique to this model. The claudin-low tumors also showed high gene expression of EMT inducers, low expression of the miR-200 family, and low to absent expression of both claudin 3 and E-cadherin. These murine subtypes also contained distinct genomic DNA copy number changes some of which are similarly altered in their cognate human subtype counterpart. Finally, limiting dilution transplantation revealed that p53 null claudin-low tumors are highly enriched for TICs as compared to the more common adenocarcinomas arising in the same model, thus providing a novel preclinical mouse model to investigate the therapeutic response of TICs.
2011-08-15 | GSE27101 | GEO
Project description:Rhabdoid Tumors (RT) are highly aggressive tumors that are frequently localized in the central nervous system (CNS) where they are termed atypical teratoid and rhabdoid tumors (ATRT). We generated conditional Smarcb1-deficient mouse model leads to CNS Smarcb1-deficient tumors. We used microarrays to compared gene expression profilings of various human and mouse tumors. Our data demonstrate that the Smarcb1-deficient mouse model recapitulates the diversity of human RT.
2016-01-27 | GSE64019 | GEO
Project description:Despite histological diversity in the subcutaneous nodules and tumors, the derived tumor-derived organoids stereotypically exhibited cystic featuresTo clarify molecular differences among the p53-null falopian tube-derived tumors driven by KrasG12D, Pik3caH1047R, and Apc580D, the transcriptome across tumor-derived organoidss, originating organoids before inoculation, p53-null organoids without driver mutations, and organoids without recombination as a reference were compared.
2021-06-30 | GSE175511 | GEO
Project description:Early T-cell precursor leukemia (ETP-ALL) is a high-risk subtype of human leukemia that is poorly understood at the molecular level. Here, we report translocations targeting the zinc finger E-box binding transcription factor ZEB2 as a new and recurrent genetic lesion in immature/ETP-ALL. Using a conditional gain-of-function mouse model, we demonstrate that sustained Zeb2 expression perturbs normal T-cell differentiation and initiates T-cell leukemia. Moreover, Zeb2 driven mouse leukemia exhibit some features of the human immature/ETPALL gene expression signature, as well as an enhanced leukemia-initiation potential and activated JAK/STAT signaling through transcriptional activation of IL7R. This study reveals ZEB2 as a novel oncogene in the biology of immature/ETP-ALL and paves the way towards pre-clinical studies of novel compounds for the treatment of this aggressive subtype of human T-ALL using our Zeb2 driven mouse model. Conditional Zeb2 knockin mouse model was developed and crossed into p53 null background. Murine T-cell leukemia/lymphoma tumors developed both in the p53 null control and the p53 null Zeb2 transgenic group. In this experiment, gene expression profiling was performed on these murine leukemias to determine the transcriptional program associated with sustained Zeb2 expression in the context of P53 null driven murine T cell leukemogenesis.
2015-05-23 | E-GEOD-62653 | biostudies-arrayexpress