Lymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused by smooth, muscle-like LAM cells which have mutations in the tumor suppressor genes Tuberous Sclerosis Complex (TSC) 1 or 2, and the capacity to metastasize. Since chemokines and their receptors function in chemotaxis of metastatic cells, we hypothesized that LAM cells may be recruited by chemokine(s) in the lung. Quantification of 25 chemokines in bronchoalveolar lavage fluid from LAM patients and healthy volunteers revealed that concentrations of MCP-1/CCL2, GROa/CXCL1 and ENA-78/CXCL5 were significantly higher in samples from LAM patients than healthy volunteers. In this transcript analysis, expression of chemokine and chemokine receptor mRNA in LAM cells differed from those in melanoma and smooth muscle cells. Subsequent immunohistochemistry of lung sections from 30 LAM patients confirmed protein expression of chemokines and these receptors varied among LAM patient and differed from that seen in breast cancer and melanoma cells. . In vitro, MCP-1/CCL2 induced selective migration of cells showing loss of heterozygosity of TSC2 from a heterogeneous populations of cells grown from explanted LAM lungs. In addition, the frequencies of single-nucleotide polymorphisms in the MCP-1 gene promoter region differed significantly in LAM patients and healthy volunteers (p=0.018), and one polymorphism was associated significantly more frequently with the decline of lung function. These observations are consistent with the notion that chemokines such as MCP-1 may serve to specify site of LAM cell metastasis.
Chemokine-enhanced chemotaxis of lymphangioleiomyomatosis cells with mutations in the tumor suppressor TSC2 gene.
Sex, Specimen part
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A macrophage gene expression signature defines a field effect in the lung tumor microenvironment.
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View SamplesAJ mouse is susceptible to lung carcinogenesis from urethane treatment and is a good model for human adenocarcinoma. We completed a study using microarray analysis of bronchoalveolar lavage cells from control or urethane treated mice. A unique macrophage expression signature in the lung tumor microenvironment was able to correctly classify the lavage samples.
A macrophage gene expression signature defines a field effect in the lung tumor microenvironment.
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View SamplesGenes regulated by the fibroblast growth factor (FGF) signalling pathway were indentified in the early development of the amphibian Xenopus laevis by comparing gene expression in control embryos and embryos in which FGF signalling was inhibited by two different dominant negative FGF receptors.
Characterisation of the fibroblast growth factor dependent transcriptome in early development.
Age, Compound, Time
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Genetic Liability for Internalizing Versus Externalizing Behavior Manifests in the Developing and Adult Hippocampus: Insight From a Meta-analysis of Transcriptional Profiling Studies in a Selectively Bred Rat Model.
Sex, Specimen part, Treatment
View SamplesThe strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This Illumina (RatRef-12v1 Beadchip) microarray study examined gene expression in the hippocampus in generation F15 male bHR rats and bLR rats at age postnatal day 14 (P14, n=6 per group).
Genetic Liability for Internalizing Versus Externalizing Behavior Manifests in the Developing and Adult Hippocampus: Insight From a Meta-analysis of Transcriptional Profiling Studies in a Selectively Bred Rat Model.
Sex, Specimen part
View SamplesIschemic tolerance can be induced by numerous preconditioning stimuli, including various Toll-like receptor (TLR) ligands. We have shown previously that systemic administration of the TLR4 ligand, lipopolysaccharide (LPS) or the TLR9 ligand, unmethylated CpG ODNs prior to transient brain ischemia in mice confers substantial protection against ischemic damage. To elucidate the molecular mechanisms of preconditioning, we compared brain and blood genomic profiles in response to preconditioning with these TLR ligands and to preconditioning via exposure to brief ischemia.
Multiple preconditioning paradigms converge on interferon regulatory factor-dependent signaling to promote tolerance to ischemic brain injury.
Specimen part, Treatment
View SamplesWe used microarrays to detail the global program of gene expression during early hESC differentiation to mesendoderm using FBS, with and without RUNX1 depletion.
Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling.
Specimen part, Cell line
View SamplesRhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. Using a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2cub/cub), which shows a regenerative phenotype, we sought to identify the underlying mechanism.
Early induction of NRF2 antioxidant pathway by RHBDF2 mediates rapid cutaneous wound healing.
Specimen part, Treatment, Time
View SamplesA QTL intercross was performed bewteen C57BL/6J and KK/HIL for albuminurea, asthma and cardiovascular related phenotypes. Several QTL were identified for most phenotypes. We performed microarray analysis from liver samples to identify genes differentially expressed between the parental strains. The results helped us narrow down the QTL and identify the candidate genes based on differential expression between the parental strains.
A major X-linked locus affects kidney function in mice.
Sex, Specimen part
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