Gene 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 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 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 SamplesTreatment of hematological malignancies by adoptive transfer of activated natural killer (NK) cells is limited by poor post-infusion persistence. We compared the ability of interleukin-2 (IL-2) and IL-15 to sustain human NK cell functions following cytokine withdrawal to model post-infusion performance. In contrasts to IL-2, IL-15 mediated stronger signaling through the IL-2/15 receptor complex and provided functional advantages. Genome-wide analysis of cytosolic and polysome-associated mRNA revealed cytokine dependent differential mRNA levels and translation during cytokine activation but also that most gene expression differences were primed by IL-15 and only manifested after cytokine withdrawal. IL-15 augmented mTOR signaling, which correlated with increased expression of genes related to cell metabolism and respiration. Consistently, mTOR inhibition abrogated IL-15-induced functional advantages. Moreover, mTOR-independent STAT-5 signaling contributed to improved NK cell function during cytokine activation but not following cytokine withdrawal. The superior performance of IL-15 stimulated NK cells was also observed using a clinically applicable protocol for NK cell expansion. Finally, expression of IL-15 correlated with cytolytic immune functions in patients with B cell lymphoma and favorable clinical outcome. These findings highlight the importance of mTOR regulated metabolic processes for immune cell functions and argue for implementation of IL-15 in adoptive NK cell cancer therapy. Overall design: Freshly isolated NK cells from 6 donors were activated with IL-2 or IL-15 for 48 hours, followed by cytokine withdrawal for 24 hours, resulting in four RNA samples per donor. From each sample, both the cytosolic as well as the polysomal fraction were collected. Donor 3 contains activation and post withdrawal data from two different donors due to poor RNA-quality obtained for some samples which did not allow for processing of the complete set of 6 donors (resulting in a total of 40 samples).
IL-15 activates mTOR and primes stress-activated gene expression leading to prolonged antitumor capacity of NK cells.
No sample metadata fields
View SamplesWe used Affymetrix HG U133 Plus 2.0 GeneChips to compare the transcriptome of miR-145-overexpressing MDA-MB-231 cells against negative control miRNA precursor-transfected cells.
miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness.
Specimen part
View SamplesExpression data of BL2 Burkitt Lymphoma cell line (controls and samples treated with different B cell specific stimuli)
Global gene expression changes of in vitro stimulated human transformed germinal centre B cells as surrogate for oncogenic pathway activation in individual aggressive B cell lymphomas.
Specimen part, Cell line
View SamplesUsing RNA-seq to identify gene expression changes after genetic deletion of ADAR Overall design: RNA-seq of A549, HCC366, NCI-H1650, and NCI-H196 cells after CRISPR-Cas9-mediated deletion of ADAR as compared to a control gene. A549 cells were also treated with vehicle or interferon-ß for 24 hours prior to collection for RNA-seq.
Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells.
Cell line, Treatment, Subject
View SamplesChronic liver injury triggers complications such as liver fibrosis and hepatocellular carcinoma (HCC), which are associated with alterations in distinct signaling pathways. Of particular interest is the interaction between mechanisms controlled by IKK/NEMO, the regulatory IKK subunit, and Jnk activation for directing cell death and survival. In the present study, we aimed to define the relevance of Jnk in hepatocyte-specific NEMO knockout mice (NEMOhepa), a genetic model of chronic inflammatory liver injury. We generated global Jnk1-/-/NEMOhepa and Jnk2-/-/NEMOhepa mice by crossing NEMOhepa mice with Jnk1-/- and Jnk2-/- animals, respectively, and examined the progression of chronic liver disease. Moreover, we investigated the expression of Jnk during acute liver injury, evaluated the role of Jnk1 in bone marrow-derived cells, and analyzed the expression of NEMO and pJnk in human diseased-livers. Deletion of Jnk1 significantly aggravated the progression of liver disease, exacerbating apoptosis, compensatory proliferation and carcinogenesis in NEMOhepa mice. Jnk2-/-/NEMOhepa showed increased RIP-1 and RIP-3 expression and hepatic inflammation. Jnk1 in hematopoietic cells rather than hepatocytes had an impact on the progression of chronic liver disease in NEMOhepa livers. These findings are of clinical relevance since NEMO expression was down-regulated in hepatocytes of patients with HCC whereas NEMO and pJnk were expressed in a large amount of infiltrating cells. While Jnk1 is protective in NEMOhepa-depleted hepatocytes, Jnk1 in hematopoietic cells rather than hepatocytes is a crucial driver of hepatic injury. These results elucidate the complex function of Jnk in chronic inflammatory liver disease.
Haematopoietic cell-derived Jnk1 is crucial for chronic inflammation and carcinogenesis in an experimental model of liver injury.
Sex, Age, Specimen part
View SamplesWe used Affymetrix HG U133 Plus 2.0 GeneChips to compare the transcriptome of HS3ST2-transfected and control vector-transfected MDA-MB-231 cells.
HS3ST2 modulates breast cancer cell invasiveness via MAP kinase- and Tcf4 (Tcf7l2)-dependent regulation of protease and cadherin expression.
Specimen part, Cell line
View Samples10 day old seedlings were treated with 5uM of the cytokinin Benzyladenine(BA)or DMSO at 15min, 45min, 120min, 480min and 1440min
Expression profiling of cytokinin action in Arabidopsis.
Age, Compound, Time
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