The ecto-enzyme CD38 is a marker of unfavorable prognosis for chronic lymphocytic leukemia (CLL) patients and an indicator of activation and proliferation of leukemic cells. Here we show that CD38 is enzymatically active in primary CLL cells and that its forced expression increases disease aggressiveness in a xenograft model. The effect is completely lost when using an enzyme deficient version of CD38 with a single amino-acid mutation. Through the enzymatic conversion of NAD, CD38 increases cytoplasmic Ca2+ concentrations, positively influencing proliferation, chemotaxis, adhesion and matrix digestion. Inhibition of the enzymatic activities of CD38 using the flavonoid kuromanin blocks CLL homing. In a short-term xenograft model using primary cells, kuromanin treatment traps CLL cells in the blood, increasing responses to chemotherapy.
The enzymatic activities of CD38 enhance CLL growth and trafficking: implications for therapeutic targeting.
No sample metadata fields
View SamplesRecent genetic studies in mice have established a key role for the nuclear receptor coregulator Trim24 in liver tumor suppression and provided evidence that Trim24 suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor alpha (Rara)-dependent transcription and cell proliferation. However, it is unknown which downstream targets of Rara regulated by Trim24 are critical for tumorigenesis. We report here that loss of Trim24 results in the overexpression of interferon (IFN)/STAT pathway genes in the liver, a process that occurs early in tumorigenesis and is more pronounced in tumors, despite the enhanced expression, late in the disease, of negative regulators such as Usp18, Socs1 and Socs2.
Tripartite motif 24 (Trim24/Tif1α) tumor suppressor protein is a novel negative regulator of interferon (IFN)/signal transducers and activators of transcription (STAT) signaling pathway acting through retinoic acid receptor α (Rarα) inhibition.
Specimen part
View SamplesWe compared the transcriptome in E16.5 embryonic mouse cortex isolated by microdissection, in control (+/+) mice and in mice with mutation in frizzled3 (Fzd3) and Celsr3. Overall design: Triplicate RNA samples prepared for each genotype
Feedback regulation of apical progenitor fate by immature neurons through Wnt7-Celsr3-Fzd3 signalling.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes.
Cell line
View SamplesHeterochromatin-protein 1 (HP1) is a functionally diverse family of proteins. In particular, Drosophila dHP1c forms a complex with the transcription factors WOC and ROW (dHP1EU) that localizes at euchromatin and regulates gene expression.
dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Specimen part, Cell line
View SamplesThe newly identified claudin-low subtype of cancer is believed to represent the most primitive breast malignancies, having arisen from transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this hypothesis, we show both in vitro and in vivo that transcription factors inducing epithelial-mesenchymal transition can drive the development of claudin-low tumors from differentiated mammary epithelial cells, by playing a dual role in cell transformation and dedifferentiation.
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Specimen part, Cell line
View SamplesThe newly identified claudin-low subtype of cancer is believed to represent the most primitive breast malignancies, having arisen from transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this hypothesis, we show both in vitro and in vivo that transcription factors inducing epithelial-mesenchymal transition can drive the development of claudin-low tumors from differentiated mammary epithelial cells, by playing a dual role in cell transformation and dedifferentiation.
EMT inducers catalyze malignant transformation of mammary epithelial cells and drive tumorigenesis towards claudin-low tumors in transgenic mice.
Specimen part, Cell line
View Samplesaffy_popsec_nancy_roots_poplar - This project aims to identify genes of interest for water deficit acclimation and/or adaptation in a tree species: poplar. We look for genes and gene expression networks related to drought stress. We intend to analyse the transcriptome in root apices, in two genotypes, Carpaccio and Soligo, at various stages and intensities of stress. Root apex is the location of root elongation and these analyses intend to identify genes involved in the control of cell expansion and thus of root elongation. Indeed, root growth maintenance in response to water shortage contributes to plant tolerance to water deficit. The comparison between medium and severe stress intensities and between early and long term stresses will power the selection of genes of interest. The co-analysis of two genotypes of contrasted tolerance to water deficit should help to better discriminate genes presenting a potential adaptative character from genes responding passively to the constraint.-Two poplar clones, Soligo (S) and Carpacio (C) were submitted to 4 treatments: control, mild water deficit, moderate water deficit (12-day long for both) and early-drought stress (about 36-h long). Growth and physiology was characterised on a batch of plants and samples collected on another batch of plants. Four to eight root apices (1cm-long) were collected on each individual tree. Total RNAs were extracted from all roots for each tree individually. Two pools of 3 (or 2) individuals were made using equimolar ratio. A pool is considered as one biological replicate and corresponds to one Affymetrix slide. The two biological replicates originate from the same experiment.
Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes.
Specimen part
View Samplesaffy_popsec_nancy_leaves_poplar - affy_popsec_nancy_leaves2007_poplar - This project aims to identify genes of interest for water deficit acclimation and/or adaptation in a tree species: poplar. We look for genes and gene expression networks related to drought stress. We intend to analyse the transcriptome in mature leaves, in two genotypes, Carpaccio and Soligo, at various stages and intensities of stress. During water deficit, leaves underwent many processes aiming to maintain cells integrity such as water status adjustment through osmoregulation or cell detoxication. These analyses intend to identify genes of interest involved in homeostasis maintenance. The comparison between medium and severe stress intensities and between early and long term stresses will power the selection of genes of interest. The co-analysis of two genotypes of contrasted tolerance to water deficit should help to discriminate genes presenting a potential adaptative character from genes responding passively to the constraint-In a first experiment, two poplar clones, Soligo (S) and Carpacio (C) were submitted to 4 treatments: control, mild water deficit, moderate water deficit (12-day long for both) and early-drought stress (about 36-h long). Growth and physiology was characterised on a batch of plants and samples collected on another batch of plants. In a second experiment, two poplar clones, Soligo (S) and Carpacio (C) were submitted to 2 treatments: control and moderate water deficit. Mature leaves were collected and total RNAs were extracted from each tree individually. Two pools of 3 (or 2) individuals were made using equimolar ratio. A pool is considered as one biological replicate and corresponds to one Affimetrix slide.
Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes.
Specimen part
View Samples