ARC (NSC 188491, SMA-491), 4-amino-6-hydrazino-7-beta-d-ribofuranosyl-7H-pyrrolo-(2,3-d)-pyrimidine-5-carboxamide, is a nucleoside analog with profound in vitro anti-cancer activity. First identified in a high-throughput screen for inhibitors of p21 mRNA expression, subsequent experiments showed that ARC also repressed expression of hdm2 and survivin, leading to its classification as a global inhibitor of transcription 1. The following Hu U133 plus 2.0 arrays represent single time point (24 hour) gene expression analysis of transcripts altered by ARC treatment. Arrays for the other compounds (sangivamycin and doxorubicin) are included as comparators.
ARC (NSC 188491) has identical activity to Sangivamycin (NSC 65346) including inhibition of both P-TEFb and PKC.
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View SamplesGene expression analysis under normal culture conditions (RPMI-10%FBS) and at optimal cell densities.
Low-risk susceptibility alleles in 40 human breast cancer cell lines.
Cell line
View SamplesThis series represents bone marrow aspirates from smoldering multiple myeloma patients
Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis.
No sample metadata fields
View SamplesWe performed whole transcriptome sequencing of human monocytes that were co-cultured with estrogen receptor positive (ER+) or triple-negative (TNBC) breast cancer cell lines and studied the biological responses related to the differential gene activation in both cell types to understand how different cancer cells educate host cells to support tumor growth Overall design: To characterize the differences in macrophage activation under the influence of either ER+ or TNBC breast cancer cells, we cultured freshly isolated human peripheral monocytes with two breast cancer cell lines (T47D, ER+ and MDA-MB-231, TNBC) in an in vitro transwell co-culture assay. The transwell setting allowed us to investigate the effect of soluble mediators on macrophage activation since direct cell contact of these cells was inhibited by a (PET) membrane (pore size 0.4 µm).
Transcriptional profiling of macrophage and tumor cell interactions in vitro.
No sample metadata fields
View SamplesETS1 and RAS/ERK regulate a common gene expression program in establishing enviroment suitable for prostate cancer cell migration. Overall design: mRNA profiles of luciferase knockdown (WT), ETS1 knockdown, and U0126 treated DU145 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.
Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2.
No sample metadata fields
View SamplesLoss of E2F transcription factos alters metastatic capacity of MMTV-PyMT tumors.
Histological subtypes of mouse mammary tumors reveal conserved relationships to human cancers.
Disease
View SamplesWe used microarrays to futher characterize the effects of T58A mutation in Myc on mammary tumorigenesis.
A mouse model with T58A mutations in Myc reduces the dependence on KRas mutations and has similarities to claudin-low human breast cancer.
Specimen part
View SamplesPBMC from house dust mite (HDM) sensitized atopics with or without asthma (or nonallergic controls) were cultured in the presence or absence of HDM extract for 24 hours.
Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.
Specimen part, Disease stage, Subject
View SamplesAdvances in genomic signatures have begun to dissect breast cancer heterogeneity, and application of these signatures will allow the prediction of which pathways are important in tumor development. Here we used genomic signatures to predict involvement of specific E2F transcription factors in Myc-induced tumors. We genetically tested this prediction by interbreeding Myc transgenics with mice lacking various activator E2F alleles. Tumor latency decreased in the E2F1 mutant background and significantly increased in both the E2F2 and E2F3 mutants. Investigating the mechanism behind these changes revealed a reduction in apoptosis in the E2F1 knockout strain. E2F2 and E2F3 mutant backgrounds alleviated Myc effects on the mammary gland, reducing the susceptible tumor target population. Gene expression data from tumors revealed that the E2F2 knockout background resulted in fewer tumors with EMT, corresponding with a reduction in probability of Ras activation. In human breast cancer we found that a low probability of E2F2 pathway activation was associated with increased relapse-free survival time. Together these data illustrate the predictive utility of genomic signatures in deciphering the heterogeneity within breast cancer and illustrate the unique genetic requirements for individual E2Fs in mediating tumorigenesis in both mouse models and human breast cancer.
Prediction and genetic demonstration of a role for activator E2Fs in Myc-induced tumors.
Specimen part
View SamplesSTEAP4 is a plasma membrane metallo-reductase involved in the transport of iron and copper. Recently, STEAP4 was implicated in promoting insulin sensitivity by acting in white adipose tissue (WAT) to control the production of inflammatory cytokines such as IL-6. Indeed, the loss of STEAP4 expression in mice leads to increased production of inflammatory cytokines in visceral WAT and systemic insulin resistance. In this report, we demonstrate that in mouse liver STEAP4 is produced at significant levels and that STEAP4 transcription is induced by IL-6. We further demonstrate that the STEAP4 gene is a direct target of phosphorylated STAT3 in mouse liver. In addition, hepatic STEAP4 expression is regulated by feeding and fasting, and obesity leads to the induction of STEAP4 expression in the liver. Interestingly, the regulation of STEAP4 in both feeding and fasting and the obese state appears to require the transcription factor C/EBPalpha that may act in concert with STAT3 as they both bind to the proximal STEAP4 promoter in vivo. Taken together these data suggest the transcriptional regulation of hepatic STEAP4 may play a critical role in the response to nutritional and inflammatory stress and contribute to the protective effect of STEAP4 in vivo.
Regulation of hepatic six transmembrane epithelial antigen of prostate 4 (STEAP4) expression by STAT3 and CCAAT/enhancer-binding protein alpha.
Sex, Specimen part
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