We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53 null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in nave hosts.
Murine microenvironment metaprofiles associate with human cancer etiology and intrinsic subtypes.
Specimen part
View SamplesmiR-372-3p target identification mRNA level Overall design: Differential expression analysis 30h post transfection with miR-372-3p mimics
microRNAs with AAGUGC seed motif constitute an integral part of an oncogenic signaling network.
Specimen part, Cell line, Treatment, Subject
View SamplesIschemia exists in many diseased tissues including arthritic joints, atherosclerotic plaques and malignant tumors. Macrophages accumulate in these sites and upregulate genes in response to the hypoxia present.
Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia.
Specimen part
View SamplesVascular pericytes, an important cellular component, in the tumor microenvironment, are often associated with tumor vasculatures and their functions in cancer invasion and metastasis are poorly understood. Here we show that PDGF-BB induces pericyte fibroblast transition (designated as PFT), which significantly contributes to tumor invasion and metastasis. Gain- and loss-of-function experiments demonstrate that the PDGF-BB-PDGFR signaling promotes PFT in vitro and in in vivo tumors. Genome-wide expression analysis indicates that PDGF-BB-activated pericytes acquire mesenchymal progenitor features. Pharmacological inhibition and genetic deletion of PDGFR ablate the PDGF-BB-induced PFT. Genetic tracing of pericytes with two independent mouse strains, i.e., TN-AP-CreERT2:R26R-tdTomato and NG2:R26R-tdTomato, shows that PFT cells gains stromal fibroblast and myofibroblast markers in tumors. Importantly, co-implantation of PFT cells with less-invasive tumor cells in mice markedly promotes tumor dissemination and invasion, leading to an increased number of circulating tumor cells (CTCs) and metastasis. Our findings reveal a novel mechanism of vascular pericytes in PDGF-BB-promoted cancer invasion and metastasis by inducing PFT and thus targeting PFT may offer a new treatment option of cancer metastasis.
Pericyte-fibroblast transition promotes tumor growth and metastasis.
Specimen part
View SamplesIn the intestine, Hedgehog (Hh) signalling orchestrates epithelial homeostasis in a bidirectional loop. Differentiated enterocytes secrete the ligand leading to active downstream signaling exclusively in the stroma. In turn, Hh-driven stromal factors contribute to the control of intestinal stem cell numbers and induce epithelial differentiation.
Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth.
Sex, Specimen part
View SamplesThe miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains largely elusive. Here we examined the effects of activation of the entire miR-17-92 cluster on global protein expression in neuroblastoma cells.
The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma.
Specimen part
View SamplesTo investigate the role of DNA topoisomerases in transcription, we have studied global gene expression in Saccharomyces cerevisiae cells deficient for topoisomerases I and II and performed single-gene analyses to support our findings. The genome-wide studies show a general transcriptional down-regulation upon lack of the enzymes, which correlates with gene activity but not gene length. Furthermore, our data reveal a distinct subclass of genes with a strong requirement for topoisomerases. These genes are characterized by high transcriptional plasticity, chromatin regulation, TATA box presence, and enrichment of a nucleosome at a critical position in the promoter region, in line with a repressible/inducible mode of regulation. Single-gene studies with a range of genes belonging to this group demonstrate that topoisomerases play an important role during activation of these genes. Subsequent in-depth analysis of the inducible PHO5 gene reveals that topoisomerases are essential for binding of the Pho4p transcription factor to the PHO5 promoter, which is required for promoter nucleosome removal during activation. In contrast, topoisomerases are dispensable for constitutive transcription initiation and elongation of PHO5, as well as the nuclear entrance of Pho4p. Finally, we provide evidence that topoisomerases are required to maintain the PHO5 promoter in a superhelical state, which is competent for proper activation. In conclusion, our results reveal a hitherto unknown function of topoisomerases during transcriptional activation of genes with a repressible/inducible mode of regulation
DNA Topoisomerases maintain promoters in a state competent for transcriptional activation in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesRat has been treated with different compounds with the purpose of investigating toxicological mechanisms. But toxic and non-toxic compounds has been administered. 3 toxic (ANIT, DMN, NMF) 3 non-tox (Caerulein, dinitrophenol(DNP), Rosiglitazone) in 5-plicates (30 arrays in all) and 9 untreated (control), 39 samples in all.
Integration of clinical chemistry, expression, and metabolite data leads to better toxicological class separation.
No sample metadata fields
View SamplesGene expression analysis of yw follicles at S9/10a, S10B, S12, and S14; Gene expression analysis of pxt mutant follicles (f01000 and EY03052) at S10B, S12, S14
Drosophila eggshell production: identification of new genes and coordination by Pxt.
Sex, Specimen part
View SamplesWe sequenced mRNA from subcuteneous adipose tissue of 36 pigs (12 Low, 12 Mean and 12 High) to investigate expression profiling of obesity (porcine model) Overall design: Examination of mRNA levels in different obese states in a porcine model for human obesity
An integrative systems genetics approach reveals potential causal genes and pathways related to obesity.
Sex, Specimen part, Subject
View Samples