We here show that loss of imprinting (LOI) of IGF2 is a frequent and early event in the development of colon cancer and occurs throughout the large intestine. LOI leads to AKT1-dependent activation and suppression of a defined set of genes, many of which are cell cycle related. Our results further showed that IGF2 induces non-canonical wnt signaling. We hypothesize that IGF2 and Wnt5a cooperate in cancer progression. LOI is an attractive target for tumor prevention or targeted therapy.
Carcinoma of the colon and rectum with deregulation of insulin-like growth factor 2 signaling: clinical and molecular implications.
Specimen part
View SamplesExisting controversy regarding the importance of AMP-activated protein kinase (AMPK) in fatty acid (FA) oxidation in skeletal muscle with contraction/exercise may to some extent pertain to redundant AMPK1 signaling. Using a mouse model lacking both AMPK1 and -2 in skeletal muscle specifically (mdKO) we hypothesized that FA utilization would be impaired in skeletal muscle. Calorimetric analysis showed a similar respiratory exchange ratio (RER) of AMPK WT and mdKO mice when fed normal chow, a high fat diet or with prolonged fasting. Though, in vivo treadmill exercise at the same relative intensity induced a higher RER in mdKO mice compared to WT (WT=0.81; mdKO=0.87; p<0.01) indicating a decreased utilization of FA. Ex vivo incubation of soleus muscle revealed that basal and contraction-induced FA oxidation was impaired in mdKO mice, suggesting that the increased RER during in vivo running exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 and FABPpm (by 17-40%) together with abolishment of TBC1D1 Ser237 phosphorylation in mdKO mice, may result in lower FA transport capacity and FA transport protein translocation to sarcolemma, respectively. In summary this study shows that the catalytically active AMPK subunits are required for normal stimulation of FA utilization during exercise and contractions.
AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice.
Specimen part
View SamplesWe observed robust overexpression of type I interferon (IFN)inducible genes and genomic signatures that indicate T cell and dendritic cell infiltration in lesional skin. Up-regulation of mRNAs for IFN-a subtypes was observed in lesional skin compared with nonlesional skin. Enrichment of mature dendritic cells and 2 type I IFNinducible proteins, STAT1 and ISG15, were observed in the majority of lesional skin biopsies. Concordant overexpression of IFN-c and TNF-ainducible gene signatures occurred at the same disease sites.
Type I interferon: potential therapeutic target for psoriasis?
Disease
View SamplesGene expression profile of cancer cell lines of breast, lung, pancreatic, gasctric, ovarian, hepatocellular, prostate carcinomas and melanomas.
Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations.
No sample metadata fields
View SamplesZebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing.
A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.
Compound
View SamplesIn order to understand differentially regulated gene expression after the different treatments, 4 size matched tumors of each group were analyzed by microarrays.
Regulation of myeloid cells by activated T cells determines the efficacy of PD-1 blockade.
Specimen part
View SamplesIn order to identify targets of the transcription factor AUXIN RESPONSE FACTOR5 / MONOPTEROS (ARF5/MP), we compared transcriptomes of mp-B4149 mutant seedlings (9 day-old) and seedlings carrying the dexamethasone-inducible version of the MP inhibitor protein BODENLOS (GR-bdl). Without dexamethasone (DEX) treatment, this line is identical to the wild-type, while DEX treatment leads to strong inhibition of ARF-dependent transcription. To remove all endogenous MP-inhibiting Aux/IAA proteins, we treated mp or GR-bdl seedlings during 1 hour with auxin (50 micromolar Indole-3-Acetic Acid), either with or without a pretreatment with 10 micromolar DEX for 1 hour. Genes that are activated by MP are expected to br downregulated in mp seedlings and in the GR-bdl line afer DEX treatment. We used biological duplicates for each of the three treatments.
MONOPTEROS controls embryonic root initiation by regulating a mobile transcription factor.
No sample metadata fields
View SamplesIllumina RNA sequencing to study DEGs between freshly isolated and emigrated skin T cells Overall design: skin T cell RNA profile of freshly isolated T cells and emigrated T cells under IL-2, IL-4, TGF-beta and IL-2, IL-15 cytokine condition
The cytokine environment influence on human skin-derived T cells.
Specimen part, Subject
View SamplesWe sequenced dorsal root ganglia mRNA from 25 BXD recombinant inbred mouse strains to determine their variation in gene expression. Overall design: Dorsal root ganglia mRNA profiles of recombinant inbred mouse strains
HTR7 Mediates Serotonergic Acute and Chronic Itch.
No sample metadata fields
View SamplesNOTCH1 is mutationally activated in ~15% of cases of chronic lymphocytic leukaemia (CLL), but its role in B-cell development and leukemogenesis is not known. Here, we report that the active intracellular portion of NOTCH1 (ICN1) is detectable in ~50% of peripheral blood CLL cases lacking gene mutations. We identify a ‘NOTCH1 CLL gene expression signature’ in CLL cells, and show that this signature is significantly enriched in primary CLL cases expressing ICN1, independent of NOTCH1 mutation. NOTCH1 target genes include key regulators of B-cell proliferation, survival and signal transduction physiology. In particular, we show that MYC is a direct target of NOTCH1 via B-cell specific distal regulatory elements, thus implicating this oncogene in the pathogenesis of the disease. Overall design: RNA-Seq analysis
Common nonmutational <i>NOTCH1</i> activation in chronic lymphocytic leukemia.
Specimen part, Subject
View Samples