Here we show that tumor necrosis factor (TNF) induced in human T-regulatory cells (Treg), as compared to conventional T cells (Tcon), a transcription program highly enriched for typical NF-B target genes, such as: the cytokines LTA and TNF; the TNF-receptor super family members FAS, 4-1BB and OX-40; various anti-apoptotic genes; and other important immune-response genes.
TNF activates a NF-kappaB-regulated cellular program in human CD45RA- regulatory T cells that modulates their suppressive function.
Specimen part, Treatment
View SamplesSOCS1 plays a role in cellular senescence. Knocking down SOCS1 in senescence induced by the STAT5 oncogene results in senescence bypass by preventing p53 activation
SOCS1 regulates senescence and ferroptosis by modulating the expression of p53 target genes.
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View SamplesExpression data from xenograft in BALB/c 6-wk-old nude mice with PC3 prostate cancer cells stably expressing PML or a vector control after treatment of the mice with palbociclib (100mg/kg/day diluted in sodium lactate 50mM pH4 given by gavage) during 5 consecutive days
A CDK4/6-Dependent Epigenetic Mechanism Protects Cancer Cells from PML-induced Senescence.
Specimen part, Cell line
View SamplesThe expression of the forkhead transcription factor CHES1, also known as FOXN3, is reduced in many types of cancers. In vitro, CHES1 expression suppresses cell proliferation in tumor cell lines but not in normal cells. Conversely shRNA-mediated depletion of CHES1 increases tumor cell proliferation.
CHES1/FOXN3 regulates cell proliferation by repressing PIM2 and protein biosynthesis.
Cell line
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Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features.
Specimen part, Cell line
View SamplesAlcoholism is associated with breast cancer incidence and progression, and moderate chronic consumption of ethanol is a risk factor. The mechanisms involved in alcohol's oncogenic effects are unknown, but it has been speculated that they may be mediated by acetaldehyde. Here, we use the immortalized normal human epithelial breast cell line MCF-12A to determine whether short- or long-term exposure to ethanol or to acetaldehyde, using in vivo compatible ethanol concentrations, induces their oncogenic transformation and/or the acquisition of epithelial mesenchymal transition (EMT). Cultures of MCF-12A cells were incubated with 25 mM ethanol or 2.5 mM acetaldehyde for 1 week, or with lower concentrations (1.0-2.5 mM for ethanol, 1.0 mM for acetaldehyde) for 4 weeks. In the 4 wk incubation, cells were also tested for anchorage independence, including isolation of soft agar selected cells (SASC) from the 2.5 mM ethanol incubations. Cells were analyzed by immuno-cytofluorescence, flow cytometry, western blotting, DNA microarrays, RT/PCR, and assays for miRs. We found that short-term exposure to ethanol, but not, in general, to acetaldehyde, was associated with transcriptional upregulation of the metallothionein family genes, alcohol metabolism genes, and genes suggesting the initiation of EMT, but without related phenotypic changes. Long-term exposure to the lower concentrations of ethanol or acetaldehyde induced frank EMT changes in the monolayer cultures and in SASC as demonstrated by changes in cellular phenotype and mRNA expression. This suggests that low concentrations of ethanol, with little or no mediation by acetaldehyde, induce EMT and some traits of oncogenic transformation such as anchorage independence in normal breast epithelial cells.
Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features.
Specimen part, Cell line
View SamplesAlcoholism is associated with breast cancer incidence and progression, and moderate chronic consumption of ethanol is a risk factor. The mechanisms involved in alcohol's oncogenic effects are unknown, but it has been speculated that they may be mediated by acetaldehyde. Here, we use the immortalized normal human epithelial breast cell line MCF-12A to determine whether short- or long-term exposure to ethanol or to acetaldehyde, using in vivo compatible ethanol concentrations, induces their oncogenic transformation and/or the acquisition of epithelial mesenchymal transition (EMT). Cultures of MCF-12A cells were incubated with 25 mM ethanol or 2.5 mM acetaldehyde for 1 week, or with lower concentrations (1.0-2.5 mM for ethanol, 1.0 mM for acetaldehyde) for 4 weeks. In the 4 wk incubation, cells were also tested for anchorage independence, including isolation of soft agar selected cells (SASC) from the 2.5 mM ethanol incubations. Cells were analyzed by immuno-cytofluorescence, flow cytometry, western blotting, DNA microarrays, RT/PCR, and assays for miRs. We found that short-term exposure to ethanol, but not, in general, to acetaldehyde, was associated with transcriptional upregulation of the metallothionein family genes, alcohol metabolism genes, and genes suggesting the initiation of EMT, but without related phenotypic changes. Long-term exposure to the lower concentrations of ethanol or acetaldehyde induced frank EMT changes in the monolayer cultures and in SASC as demonstrated by changes in cellular phenotype and mRNA expression. This suggests that low concentrations of ethanol, with little or no mediation by acetaldehyde, induce EMT and some traits of oncogenic transformation such as anchorage independence in normal breast epithelial cells.
Long-term exposure of MCF-12A normal human breast epithelial cells to ethanol induces epithelial mesenchymal transition and oncogenic features.
Specimen part, Cell line
View SamplesThe robust and consistent expression of the CD13 cell surface marker on very early as well as differentiated myeloid hematopoietic cells has prompted numerous investigations seeking to define roles for CD13 in myeloid cells. To directly address the function of myeloid CD13 we created a CD13 null mouse and assessed the responses of purified primary macrophages or dendritic cells from wild type and CD13 null animals in cell assays and inflammatory disease models where CD13 has been previously implicated. We find that mice lacking CD13 develop normally with normal hematopoietic profiles. Moreover, in in vitro assays, CD13 appears to be largely dispensable for the aspects of phagocytosis, proliferation and antigen presentation that we tested, but may contribute to adhesion to endothelial cells. In vivo assessment of four inflammatory disease models showed that lack of CD13 has little effect on disease onset or progression. Nominal alterations in gene expression levels between CD13 wild type and null macrophages argue against compensatory mechanisms. Analysis of the dataset with Ingenuity Pathway Analysis software did not suggest that loss of CD13 resulted in a purturbation of any specific biological pathways, processes or networks. Therefore, while CD13 is highly expressed on myeloid cells and is a reliable marker of the myeloid lineage of both normal and leukemic cells, it is not a critical regulator of hematopoietic development, hemostasis or myeloid cell function.
CD13 is dispensable for normal hematopoiesis and myeloid cell functions in the mouse.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Long-term exposure of MCF-7 breast cancer cells to ethanol stimulates oncogenic features.
Specimen part, Cell line
View SamplesWe analyze the contribution of alternative splicing to the transcriptional complexity in adipose tissue and the development of diet-induced obesity. Overall design: We use Next generation sequencing analysis of eWAT from control and Nova1 and Nova2-deficient mice fed with a control diet
An alternative splicing program promotes adipose tissue thermogenesis.
Sex, Age, Specimen part, Cell line, Subject
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