Purpose: To determine early changes in gene expression that drive gastric cancer development in the landscape of CLDN18 loss using RNAseq. Results: Although claudin-18 is a tight junction protein and should regulate paracellular permeabiity and/or ion flux across the mucosa, we showed this protein is rather a potent tumor suppressor that regulates cellular signaling and differentiation pathways in gastric epithelial cells. Methods: Stomach neck region mRNA profiles of 7-day-old wild-type (WT) and claudin-18 knockout (CLDN18-/-) mice were generated by deep sequencing, in triplicate, using the Illumina HiSeq2000 sequencing system. The resulting sequences were mapped to the Mouse genome (mm10) using STAR aliger and P-values were adjusted using the Benjamini-Hochberg procedure (J R Statist Soc B 1995;57:289-300). Conclusions: Loss of claudin-18 promotes gastric cancer development by modulating the expression program of gastric epithelial cells, including cellular signaling and differentiation pathways that are required for mucosal homeostasis. Overall design: Stomach (neck region only) mRNA profiles of 7-day old wild-type (WT) and CLDN18-/- mice were generated by deep sequencing, in triplicate, using an Illumina HiSeq2000 sequencing system.
Loss of Tight Junction Protein Claudin 18 Promotes Progressive Neoplasia Development in Mouse Stomach.
Age, Cell line, Subject
View SamplesWe are investigating the transcriptional response of mice infected with Helicobacter hepaticus and links to liver cancer
Genetic susceptibility to chronic hepatitis is inherited codominantly in Helicobacter hepaticus-infected AB6F1 and B6AF1 hybrid male mice, and progression to hepatocellular carcinoma is linked to hepatic expression of lipogenic genes and immune function-associated networks.
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View SamplesmRNA expression in colon cancer tumores
Mice that express human interleukin-8 have increased mobilization of immature myeloid cells, which exacerbates inflammation and accelerates colon carcinogenesis.
Sex, Specimen part
View SamplesThe gene expression of murine splenic myeloid derived suppressor cells treated with Tff2 is characterized. The motivation of the study originates in the fact that Gr1+Cd11b+ myeloid-derived suppressor cells (MDSCs), which resemble immature myeloid cells (IMCs), expand during cancer in response to inflammatory cytokines and accumulate in the spleen. MDSCs promote neoplastic progression through their suppression of anti-tumourigenic cytotoxic T-cells. MDSCs are also rapidly expanded following acute insults, but in cancer as opposed to acute inflammation, MDSCs persist. It is now recognized that a vagally-mediated, anti-inflammatory reflex arc promoting acetylcholine secretion by Cd4+ (Cd44hiSelllo) T cells, is necessary for a return to homeostasis after an acute insult. Failure of this restorative neural circuit might contribute to unabated procarcinogenic inflammation, with the chronic expansion of MDSCs driving carcinogenesis. Trefoil factor 2 (Tff2) is a secreted anti-inflammatory peptide produced by both epithelial cells and a small subset of splenic T cell.
Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer.
Sex, Age, Specimen part
View SamplesThe gene expression of bone marrow cells of mice enriched for
Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.
Sex, Specimen part
View SamplesIn these microarray experiments, we characterize the gene expression of mammary epithelial cells (MCF10A cells) grown in either a traditional monolayer cell culture setting (2D) or on Matrigel, which induces single MCF10A cells to form organized acinar structures (3D). Morphogenesis of mammary epithelial cells into organized acinar structures in vitro is accompanied by widespread changes in gene expression patterns, including a substantial decrease in expression of Myc.
Epithelial cell organization suppresses Myc function by attenuating Myc expression.
Specimen part, Cell line, Time
View SamplesTCL1 is an an oncogene and transgenic (Tg) mice expressing TCL1 specifically in B-cells are well-characterized models for chronic lymphocytic leukemia. On the contrary, PTPROt is a phosphatase with tumor suppressor characteristics in many cancers including leukemia. Our hypothesis was that transgenic expression of PTPROt in the B-cells of TCL1 Tg mice will alleviate disease phenotype and allow the study of the in vivo mechanism of action of PTPROt. To test this we have generated Tg mice with B-cell specific expression of PTPROt and crossed these mice with the TCL1 Tg mice.
PTPROt-mediated regulation of p53/Foxm1 suppresses leukemic phenotype in a CLL mouse model.
Sex, Specimen part
View SamplesMalignant melanoma is a common and frequently lethal disease. Current therapeutic interventions have little effect on survival, emphasizing the need for a better understanding of the genetic, epigenetic, and phenotypic changes in melanoma formation and progression. We identified genes that were not previously known to be silenced by methylation in melanoma using a microarray-based screen following treatment of melanoma cell lines with the DNA methylation inhibitor 5-Aza-2'-deoxycytidine.
Epigenetic silencing of novel tumor suppressors in malignant melanoma.
No sample metadata fields
View SamplesBackground:
Natural variants of AtHKT1 enhance Na+ accumulation in two wild populations of Arabidopsis.
Specimen part
View SamplesThese data show distinct interactions between these two drugs on CLL cells in vitro with an ex vivo treatment
Lenalidomide Induces Interleukin-21 Production by T Cells and Enhances IL21-Mediated Cytotoxicity in Chronic Lymphocytic Leukemia B Cells.
Specimen part, Treatment, Subject
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