In pancreatic cancer the survival rate is low, as the available treatment options usually only extend survival and seldom produce a cure. Drug resistance and disease reoccurrence is the typical reason for death after cancer diagnosis. 5-Fluorouracil (5-FU) is the main chemostatic used in first line therapy. However the majority of the tumors become resistant to treatment. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc03.27 cell line by long-term exposure to 5-FU. In addition to increased expression of markers associated with multidrug resistance, the 5-FU resistant clones showed alterations typical of the process of epithelial-to-mesenchymal transition (EMT), including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, which was confirmed on RNA and protein levels. Expression of the adhesion molecule L1CAM is associated with a chemoresistant and migratory phenotype of pancreatic cancer. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with monoclonal antibodies, we discovered that the increased invasiveness observed in the chemoresistant cells depends on L1CAM. Using esiRNA targeting -catenin and/or Slug, we discovered that L1CAM expression depends on Slug rather than -catenin in the 5-FU resistant cells. We demonstrate a functional link between Slug and the expression level of L1CAM in pancreatic cancer cells having undergone EMT following long-term exposure to 5-FU. Our findings provide further insight into the molecular mechanisms leading to a chemoresistant and migratory phenotype in pancreatic cancer cells and indicate the importance of Slug-induced L1CAM in refractory pancreatic cancer.
Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment.
Cell line
View SamplesOne of the key questions in developmental biology is how from universally shared molecular mechanisms and pathways, is it possible to generate organs displaying similar or complementary functions, with a wide range of different shapes or tissue organization? The dentition represents a valuable system to address the issues of differential molecular signatures generating specific tooth types. We performed a comparative transcriptomic analysis of developing murine lower incisors, mandibular molars and maxillary molars at the developmental cap stage (E14.5) prior to recognizable tooth shape and cusp pattern.
Molars and incisors: show your microarray IDs.
Specimen part
View SamplesThe histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cells (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL (Male-Specific Lethal) and NSL (Non-specific lethal). The individual contribution of MSL and NSL complexes to transcription regulation in mESCs is not well understood. Our genome-wide analysis of MSL and NSL localization show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds at promoters, iii) while MSL binds in gene bodies. Knockdown of Msl1 leads to a global loss of histone H4K16ac indicating that MSL is the main HAT acetylating H4K16 in mESCs. MSL was enriched at many mESC-specific genes, but also at bivalent domains. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs. Furthermore, MSL is essential for the regulation of key mESC-specific and bivalent developmental genes.
Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation.
No sample metadata fields
View SamplesGene expression profiling in dopaminergic brain structures of rats self-administering cocaine. Effect of histone deacetylase inhibition
Inhibition of histone deacetylases in rats self-administering cocaine regulates lissencephaly gene-1 and reelin gene expression, as revealed by microarray technique.
Sex, Specimen part, Treatment
View SamplesBulk RNA-seq to profile of c-kit+ cardiac interstitial cells, comparing the transcriptomes of Pim-1 enhanced cardiac progenitor cells and transfection control Overall design: Transcriptional profiling of Pim-1 enhanced human derived cardiac interstitial cells by bulk RNA-Seq
Safety profiling of genetically engineered Pim-1 kinase overexpression for oncogenicity risk in human c-kit+ cardiac interstitial cells.
Specimen part, Subject
View SamplesIntravenous Immunoglobulin (IVIg) is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyper-reactivity (AHR) and inflammation in mouse models of allergic airway disease (AAD), associated with induction of Foxp3+ regulatory T cells (Treg). Using DEREG (DEpletion of REGulatory T cell) mice, in which endogenous Treg can be ablated with Diphtheria toxin (DTx) treatment, we demonstrate that IVIg generates a de novo population of induced Treg (iTreg) in the absence of endogenous Treg. IVIg-generated iTreg were sufficient for inhibition of ovalbumin-induced AHR in an antigen-driven murine model of AAD. In the absence of endogenous Treg, IVIg failed to confer protection against AHR and airway inflammation. Adoptive transfer of purified IVIg-generated iTreg prior to antigen challenge effectively prevented airway inflammation and AHR in an antigen-specific manner.
Peripherally Generated Foxp3<sup>+</sup> Regulatory T Cells Mediate the Immunomodulatory Effects of IVIg in Allergic Airways Disease.
Specimen part
View SamplesMouse embryonic stem (ES) cells remain pluripotent in vitro when grown in presence of Leukaemia Inhibitory Factor (LIF). LIF starvation leads to apoptosis of some of the ES-derived differentiated cells, together with p38a MAP kinase activation. Apoptosis, but not morphological cell differentiation, is blocked by a p38 inhibitor, PD 169316. To further understand the mechanism of action of this compound, we have identified its specific targets by microarray studies. We report on the global expression profiles of genes expressed at three days upon LIF withdrawal (d3) compared to pluripotent cells and of genes whose expression is modulated at d3 under anti-apoptotic conditions. We showed that at d3 without LIF cells express, earlier than anticipated, specialized cell markers and that when the apoptotic process was impaired, expression of differentiation markers was altered. In addition, functional tests revealed properties of anti-apoptotic proteins not to alter cell pluripotency and a novel role for metallothionein 1 gene which prevents apoptosis of early differentiated cells.
Apoptosis and differentiation commitment: novel insights revealed by gene profiling studies in mouse embryonic stem cells.
No sample metadata fields
View SamplesSystemic lupus erythematosous (SLE) is an autoimmune disease with an important clinical and biological heterogeneity. B lymphocytes appear central to the development of SLE which is characterized by the production of a large variety of autoantibodies and hypergammaglobulinemia. In mice, immature B cells from spontaneous lupus prone animals are able to produce autoantibodies when transferred into immunodeficient mice, strongly suggesting the existence of intrinsic B cell defects during lupus. In order to approach these defects in humans, we compared the peripheral B cell transcriptomes of quiescent lupus patients to normal B cell transcriptomes.
B cell signature during inactive systemic lupus is heterogeneous: toward a biological dissection of lupus.
Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
Specimen part
View SamplesCoffinLowry Syndrome (CLS) is a syndromic form of mental retardation caused by loss of function mutations in the X-linked RPS6KA3 gene, which encodes Rsk2, a serine/threonine kinase involved in spatial memory. We analyzed hippocampal gene expression profiles in Rsk2-KO mice to identify changes in molecular pathways.
Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin-Lowry syndrome.
No sample metadata fields
View Samples