Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression changes in mouse pancreatic cancer xenograft induced by exposure to enriched environment

ABSTRACT: Previous studies reported that mice living in an enriched environment (EE) showed reduced growth of melanoma, colon and breast tumors. Our study extended the potential anti-tumor effect of EE exposure to pancreatic cancer, and firstly provided evidence demonstrating that EE exposure significantly inhibits tumor growth in a syngeneic murine model of pancreatic cancer. To further investigate the mechanisms underlying the EE-induced pancreatic tumor inhibition, we analyzed the gene expression changes in pancreatic tumor xenograft using an integrative transcriptomic and proteomic approach. Our results found that EE largely decreased the expression of genes associated with mitochondrial function at transcriptional level in pancreatic tumor, suggesting mitochondrial dysfunction in tumor cells may play a critical role in EE-induced anti-tumor phenotype. Three-week-old C57BL/6 mice were randomized to live in either enriched environment or standard environment conditions. Mice from both groups were given subcutaneous injection of Panc02 murine pancreatic cancer cells (6 M-CM-^W 105 cells per mouse) and lived in their respective homes for 5 additional weeks. Pooled RNA samples extracted from Panc02 tumors (6 mice for each group) were then subjected to Agilent-014868 Whole Mouse Genome 4M-bM-^XM-^S44k Microarray analyses.

ORGANISM(S): Mus musculus

SUBMITTER: Yu Gan

PROVIDER: E-GEOD-58306 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Gene-environment interactions mediated at the epigenetic level may provide an initial step in delivering an appropriate response to environmental changes. 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC), accounts for ~40% of modified cytosine in brain and has been implicated in DNA methylation-related plasticity. To identify the role of 5hmC in gene-environment interactions, we exposed both young (6-week-old) and aged (18-month-old) mice to both an enriched environment and a standard environment. Exposure to EE significantly improves learning and memory in aged mice and reduces 5hmC abundance in mouse hippocampus. Furthermore, we mapped the genome-wide distribution of 5hmC and found that the alteration of 5hmC modification occurred mainly at gene bodies. In particular, genes involved in axon guidance are enriched among the genes with altered 5hmC modification. These results together suggest that environmental enrichment could modulate the dynamics of 5hmC in hippocampus, which could potentially contribute to improved learning and memory in aged animals. To identify the role of 5hmC in gene-environment interactions, we exposed both young (6-week-old) and aged (18-month-old) C57B/6 mice to both an enriched environment (EE) and a standard environment. Exposure of mice to EE was achieved by keeping a group of mice in the EE chamber, which is larger than the standard cage, includes novel objects, such as toys of varied color and texture, tunnels, an exercise wheel for voluntary exercise, and extra bedding material, along with free access to food and water. Daily exposure to EE was kept at 5 hours during the daylight cycle for 4 consecutive weeks. Control animals were kept in their small cages that are used as standard housing cages (CE) containing bedding, food and access to water. YC, young mice exposing to control environment, YE, young mice exposing to enriched environment, AC, aged mice exposing to control environment, AE, aged mice exposed to enriched environment. Please note that 5hmC-containing DNA enrichment method was inspired by a unique character of beta-glucotransferase that can specifically add glucose to 5hmC modification. With a modified glucose conjugated with biotin, we are able to purify the 5hmC-containing DNA by biotin-streptavidin-based immunoprecipitation.

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Gene expression changes in mouse pancreatic cancer xenograft induced by exposure to enriched environment

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