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GSE46405
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transforming growth factor (TGF)- plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF- signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcriptionfactors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-b-induced cell motility. Knockdown of Olig1 attenuated TGF--induced cell motility in chamber migration and wound healing assays. In contrast, Olig1 knockdown had no effect on bone morphogenetic protein-induced cell motility, TGF--induced cytostasis or epithelial-mesenchymal transition. Furthermore, we observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans isomerase, Pin1. TGF-b-induced cell motility, induction of Olig1-regulated genes, and physical interaction between Smad2/3 and Olig1 were all inhibited after knockdown of Pin1, indicating a novel mode of regulation of Smad signaling. We also found that Olig1 interacts with the L3 loop of Smad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-b-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-b-induced cellular responses.
Publication Title
Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
TCL1 is an an oncogene and transgenic (Tg) mice expressing TCL1 specifically in B-cells are well-characterized models for chronic lymphocytic leukemia. On the contrary, PTPROt is a phosphatase with tumor suppressor characteristics in many cancers including leukemia. Our hypothesis was that transgenic expression of PTPROt in the B-cells of TCL1 Tg mice will alleviate disease phenotype and allow the study of the in vivo mechanism of action of PTPROt. To test this we have generated Tg mice with B-cell specific expression of PTPROt and crossed these mice with the TCL1 Tg mice.
Publication Title
PTPROt-mediated regulation of p53/Foxm1 suppresses leukemic phenotype in a CLL mouse model.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
CCRF_CEM cell line was treated by AB61 which is potent cytotoxic compound, as the positive controls were used tubercidin and actinomycin D.
Publication Title
7-(2-Thienyl)-7-Deazaadenosine (AB61), a New Potent Nucleoside Cytostatic with a Complex Mode of Action.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Total, nascent and unlabeled RNA were prepared following 1h of labeling with 100 M 4-thiouridine and 3 replicates analyzed by Affymetrix Gene ST 1.0 arrays
Publication Title
Systematic analysis of viral and cellular microRNA targets in cells latently infected with human gamma-herpesviruses by RISC immunoprecipitation assay.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
RIP-Chip was performed on DG75-eGFP, DG75-10/12, BCBL-1, BL41, BL41 B95.8 and Jijoye using anti-human Ago2 (11A9) antibodies. Anti-BrdU antibodies were used as controls for DG75-eGFP, DG75-10/12 and BCBL-1. Total RNA was used as control for BL41, BL41 B95.8 and Jijoye. Samples were analyzed on Affymetrix Gene ST 1.0 Arrays (2 independent biological replicates / sample)
Publication Title
Systematic analysis of viral and cellular microRNA targets in cells latently infected with human gamma-herpesviruses by RISC immunoprecipitation assay.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The intracellular pathogen Trypanosoma cruzi secretes an activity that blocks TGF--dependent induction of connective tissue growth factor (CTGF/CCN2). Here, we address the mechanistic basis for T. cruzi-mediated interference of
Publication Title
A soluble factor from Trypanosoma cruzi inhibits transforming growth factor-ß-induced MAP kinase activation and gene expression in dermal fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Oncogenic transformation in Ewing sarcoma tumors is driven by the fusion oncogene EWS-FLI1. The inducible expression of EWS-FLI1 (EF) in embryoid bodies, or collections of differentiating stem cells, generates cells with properties of Ewing sarcoma tumors, including characteristics of transformation. These cell lines exhibit anchorage-independent growth, a lack of contact inhibition and a strong Ewing sarcoma gene expression signature. These cells also demonstrate a requirement for the persistent expression of EWS-FLI1 for cell survival and growth.
Publication Title
Modeling the initiation of Ewing sarcoma tumorigenesis in differentiating human embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 142 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Transcript dynamics in mitotic exit mutants in the S. cerevisiae BF264-15D strain background. We examined the extent to which periodic cell-cycle transcription persisted in cells arrested in anaphase with intermediate level of B-cyclins.
Publication Title
Reconciling conflicting models for global control of cell-cycle transcription.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We identify sites of combinatorial control by performing high throughput ChIP experiments on p300, CREB-binding protein (CBP), the deacetylase SIRT1 and on multiple DNA-binding transcription factors in three different tissues. We present a quantitative model of transcriptional regulation that reveals the contribution of each binding site to tissue-specific gene expression in several mouse cell types. Binding to both evolutionarily conserved and non-conserved sequences is found to contribute significantly to transcriptional regulation. We demonstrate that binding location strongly predicts the expression level of nearby genes.
Publication Title
A quantitative model of transcriptional regulation reveals the influence of binding location on expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
Illumina HiSeq 2000
Description
The Wnt gene family is an evolutionarily conserved group of proteins that regulate cell growth, differentiation, and stem cell self-renewal. Aberrant Wnt signaling in human breast tumors has been proposed to be an attractive drug target, especially in the basal-like subtype where canonical Wnt signaling is both enriched and predictive of poor clinical outcomes. The development of effective Wnt based therapeutics, however, has been slowed in part by a limited understanding of the context dependent nature with which these aberrations influence breast tumorigenesis. We recently reported that MMTV-Wnt1 mice, which are an established model for studying Wnt signaling in breast tumors, develop two subtypes of tumors by gene expression classification: Wnt1-EarlyEx and Wnt1-LateEx. Here, we extend this initial observation and show that Wnt1-EarlyEx tumors had high expression of canonical Wnt, non-canonical Wnt, and EGFR signaling pathway signatures. Therapeutically, Wnt1-EarlyEx tumors had a dynamic reduction in tumor volume when treated with an EGFR inhibitor. Wnt1-EarlyEx tumors also had primarily Cd49fpos/Epcamneg FACS profiles, but were unable to be serially transplanted into wild-type FVB female mice. Wnt1-LateEx tumors, conversely, had a bloody gross pathology, which was highlighted by the presence of 'blood lakes' by H&E staining. These tumors had primarily Cd49fpos/Epcampos FACS profiles, but also contained a secondary Cd49fpos/Epcamneg subpopulation. Wnt1-LateEx tumors were enriched for activating Hras1 mutations and were capable of reproducing tumors when serially transplanted into wild-type FVB female mice. This study definitely shows that the MMTV-Wnt1 mouse model produces two phenotypically distinct subtypes of mammary tumors. Importantly, these subtypes differ in their therapeutic response to an EGFR inhibitor, suggesting that a subset of human tumors with aberrant Wnt signaling may also respond to erlotinib. Overall design: Agilent gene expression microarrays were performed comparing RNA from FVB/n MMTV-Wnt1 mammary tumors to a common mouse reference sample. Agilent CGH microarrays were performed comparing DNA from FVB/n MMTV-Wnt1 mammary tumors to DNA from FVB wild-type mice. RNAseq libraries were prepared from FVB/n MMTV-Wnt1 mammary tumors using a TruSeq RNA kit before being submitted to the Lineberger Comprehensive Cancer Center Genomics Core to be run on the Illumina HiSeq 2000.
Publication Title
The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor.
Sample Metadata Fields
Specimen part, Subject
View Samples