Chronic infection with the bacterial pathogen Helicobacter pylori is a risk factor for the development of gastric cancer, yet remains asymptomatic in a majority of individuals. We report here that the C57Bl6 mouse model of experimental infection with the closely related H. felis recapitulates this wide range in host susceptibility. A majority of infected mice develop premalignant lesions such as gastric atrophy, compensatory epithelial hyperplasia and intestinal metaplasia, whereas a minority is completely protected from preneoplasia. Protection is associated with the failure to mount an IFN-gamma response to the infection and an associated high Helicobacter burden. We demonstrate that IFN-gamma is essential for clearance of Helicobacter, but also mediates the formation of preneoplastic lesions. We further provide evidence that IFN-gamma triggers a specific transcriptional program in murine gastric epithelial cells in vitro and in vivo, and induces their preferential transformation to the hyperplastic phenotype. In summary, our data suggest a dual role for IFN-gamma in Helicobacter pathogenesis that could provide an explanation for the differential susceptibility to H. pylori-induced gastric pathology in the human population.
The CD4+ T cell-mediated IFN-gamma response to Helicobacter infection is essential for clearance and determines gastric cancer risk.
To determine the effect on gene expression of intratumoral injection of the Toll-like receptor agonist CpG1826. MC38 colon cancer cells were injected subcutaneously into C57BL/6 mice and allowed to establish until ~40 mm2.
Toll-Like Receptor Triggering and T-Cell Costimulation Induce Potent Antitumor Immunity in Mice.
Specimen partView Samples
Effect of FGF2 on the transcriptional profile of microvascular endothelial cells
A pro-inflammatory signature mediates FGF2-induced angiogenesis.
Specimen part, Cell line, CompoundView Samples
Psoriasin (S100A7) has been shown to be highly expressed in invasive estrogen receptor negative breast cancers. Expression of S100A7 in human breast tumors represents a poor prognostic marker and correlates with lymphocyte infiltration in high-grade morphology. Recent studies have shown that S100A7 downregulation in ER- cells lines inhibits tumor growth in in vivo mouse model systems. However, not much is known about its mechanisms in regulating breast cancers.
S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways.
Cell lineView Samples
Analysis of gene expression in lungs of C57BL/6J mice that develop chronic airway disease phenotypes after a single Sendai virus infection, compared with mice treated with UV-inactivated virus.
Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.
Sex, TimeView Samples
Transcript profiling analysis of csn4-1 light grown mutant seedlings compared to wild type using Arabidopsis ATH1 GeneChip array
Characterization of the VIER F-BOX PROTEINE genes from Arabidopsis reveals their importance for plant growth and development.
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We used microarrays to detail the global gene expression changes following apical infection of porcine choroid plexus epithelial cells (PCPEC) with Streptococcus suis (S. suis)
In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines.
Specimen partView Samples
Genome-wide association studies (GWAS) have identified dozens of genomic loci, whose single nucleotide polymorphisms (SNPs) predispose to prostate cancer (PCa). However, the biological functions of these common genetic variants and the mechanisms to increase disease risk are largely unknown. We integrated chromatin-IP coupled sequencing (ChIP-seq) and microarray expression profiling in the TMPRSS2-ERG gene rearrangement positive DuCaP cell model with the NHGRI GWAS PCa risk SNPs catalog, in an attempt to identify disease susceptibility SNPs localized within functional androgen receptor binding sites (ARBSs). Among the 48 GWAS index SNPs and 2,702 linked SNPs defined by the 1000G project 104 were found to be localized in the AR ChIP-seq peaks. Of these risk SNPs, rs11891426 T/G in the 7th intron of its host gene melanophilin (MLPH) was found located within a putative auxiliary ARE motif, which we found enriched in the neighborhood of canonical ARE motifs. Exchange of T to G attenuated the transcriptional activity of the MLPH-ARBS in a reporter gene assay. The expression of MLPH protein in tissue samples from prostate cancer patients was significantly lower in those with the G compared to the T allele. Moreover, a significant positive correlation of AR and MLPH protein expression levels was also confirmed in tissue samples. These results unravel a hidden link between AR and a functional PCa risk SNP rs11891426, whose allele alteration affects androgen regulation of its host gene MLPH. This study shows the power of integrative studies to pin down functional risk SNPs and justifies further investigations.
Putative Prostate Cancer Risk SNP in an Androgen Receptor-Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites.
Cell line, Treatment, TimeView Samples
Purpose:Next-generation sequencing has revolutionized sytems-level celluar pathway analysis. The goals of this study are to compare the U87 cell xenograft GBM mice (U87 cell line) to TWIST1 knock out U87 cell xenograft GBM mice (TWIST1 knock out U87 cell line) using their transcriptomes Overall design: Methods: Investigation of TWIST1 expression on glioblastoma malignancy in vitro and in vivo.
Targeting TWIST1 through loss of function inhibits tumorigenicity of human glioblastoma.
Specimen part, SubjectView Samples