Project description:We have created mice by performing gastric epithelium-specific knockout of common tumor suppressor genes. Mice with transgene were monitored for spontaneous gastric cancer. Gene expression profiles were obtained from fresh frozen mouse primary gastric cancer samples.
Project description:Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor that negatively regulates cell survival and proliferation by antagonizing phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt) signaling. Loss of heterozygosity (LOH) of PTEN, reduced expression of PTEN and overexpression of phosphorylated Akt are frequently found in human gastric cancer, and their changes correlate with tumor progression and prognosis. Previous studies have shown that the deregulated miRNAs in human gastric cancer play important roles in gastric cancer cell proliferation, apoptosis and inflammation. However, miRNAs downstream PTEN/Akt signaling is poorly investigated. To clarify whether PTEN is involved in gastric tumorigenesis, we have generated a gastric epithelium specific PTEN knockout mouse which exhibited gastric tumor formation with enhanced cell proliferation.So the objectives of the microarray experiment were to, a) screen miRNAs which might be regulated by PTEN/Akt signaling by comparing the miRNA expression profiles between PTEN deficient and control gastric epithelia. 2) explore the microRNA mechanism involved in gastric cell proliferation and gastric tumorigenesis. miRNA profiling of mouse gastric epithelium,comparing Pten mutant mouse with controls. 4 samples. Experiments in 2 different time point, 20 days and 60 days after birth, 2 Biological replicates. Mutant tissue vs. controls from mixture of 3-4 mouse.
Project description:Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor that negatively regulates cell survival and proliferation by antagonizing phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt) signaling. Loss of heterozygosity (LOH) of PTEN, reduced expression of PTEN and overexpression of phosphorylated Akt are frequently found in human gastric cancer, and their changes correlate with tumor progression and prognosis. Previous studies have shown that the deregulated miRNAs in human gastric cancer play important roles in gastric cancer cell proliferation, apoptosis and inflammation. However, miRNAs downstream PTEN/Akt signaling is poorly investigated. To clarify whether PTEN is involved in gastric tumorigenesis, we have generated a gastric epithelium specific PTEN knockout mouse which exhibited gastric tumor formation with enhanced cell proliferation.So the objectives of the microarray experiment were to, a) screen miRNAs which might be regulated by PTEN/Akt signaling by comparing the miRNA expression profiles between PTEN deficient and control gastric epithelia. 2) explore the microRNA mechanism involved in gastric cell proliferation and gastric tumorigenesis.
Project description:To identify chromatin alterations in primary gastric adenocarcionomas, we performed nano-scale chromatin immunoprecipitation-sequencing (Nano-CHiPseq) of histone modifications in 5 gastric cancers and matched normal tissues, We identified hundreds of somatically-altered promoters (marked by H3K4me3) and enhancers (H3K4me1). The majority of cancer-associated promoters localized to genomic sites lacking previously-annotated transcription start sites (“cryptic promoters”), driving high expression of nearby genes implicated in gastrointestinal cancers, embryonic development, and tissue specification. Our findings demonstrate the feasibility of performing chromatin profiling on solid tumors where tissue is limiting, to identify in non-coding regions regulatory elements, transcriptional patterns and genetic variants associated with cancer. We propose a pervasive role for cryptic promoters in the reactivation of early developmental programs in gastric cancer, and the potential utility of cryptic promoters as biomarkers of malignancy. Five gastric cancer tumor normal pairs are profiling in multiple number of chromatin marks
Project description:To identify chromatin alterations in primary gastric adenocarcionomas, we performed nano-scale chromatin immunoprecipitation-sequencing (Nano-CHiPseq) of histone modifications in 5 gastric cancers and matched normal tissues, We identified hundreds of somatically-altered promoters (marked by H3K4me3) and enhancers (H3K4me1). The majority of cancer-associated promoters localized to genomic sites lacking previously-annotated transcription start sites (“cryptic promoters”), driving high expression of nearby genes implicated in gastrointestinal cancers, embryonic development, and tissue specification. Our findings demonstrate the feasibility of performing chromatin profiling on solid tumors where tissue is limiting, to identify in non-coding regions regulatory elements, transcriptional patterns and genetic variants associated with cancer. We propose a pervasive role for cryptic promoters in the reactivation of early developmental programs in gastric cancer, and the potential utility of cryptic promoters as biomarkers of malignancy.
Project description:Examine methylation changes in gene promoters in gastric cancers and matched normal control gastric epithelium, using Nimblegen arrays. Direct comparison of gastric cancers and matched normal control gastric epithelium
Project description:To develop a syngeneic mouse model of metastatic gastric cancer, we established the tumor organoids from gastric tumor arising in GAstric Neoplasia (GAN) mice (GAN-WT) which express Wnt1 and the PGE2 synthesis enzymes COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) in the stomach epithelium. Furthemore, GAN-WT organoids were genetically manupilated into p53 knockout organoids (GAN-p53KO) and KrasG12V-expressing GAN-p53KO organoids (GAN-KP).
Project description:The goal of this project was to compare the metabolite profiles of the: mouse gastric antrum and the mouse gastric corpus, the mouse gastric antrum and the mouse gastric antrum isolated glands, and the mouse gastric corpus and the mouse gastric corpus isolated glands.
Project description:Gastric cancer is one of the most common cancers worldwide. Epstein-Barr virus-associated gastric cancer accounts for approximately 10% of all gastric cancers. EBV expresses its own proteins and miRNAs (BART miRNAs) and regulates host gene expression. In this study, we examined the effect of EBV infection on host mRNA expression. Differential gene expression was analyzed between EBV-negative human gastric cancer cell line AGS and EBV-positive human gastric cancer cell line AGS-EBV.
Project description:Examine methylation changes in gene promoters in gastric cancers and matched normal control gastric epithelium, using Nimblegen arrays.