Non-tumor/tumor intestinal tissue of control or intestine-specific HAI-1 deficient Apc(Min/+) mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE40856 | GEO | 2013/04/01
SECONDARY ACCESSION(S): PRJNA175120
REPOSITORIES: GEO
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:To analyse roles of HAI-1/Spint1 in intestinal tumorigenesis, we examined the effect of intestine-specific deletion of Spint1 gene on Apc(Min/+) mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in ApcMin/+ mice and shortened their survival periods. Mouse small intestine tumor tissue or background mucosa lacking macroscopically visible tumors were proceeded to RNA extraction and hybridization on microarrays (Affymetrix Mouse Genome 430 2.0 Array). Non-tumor or tumor intestinal mucosa tissues of Apc (Min/+)/Spint1 (flox/flox) mice and non-tumor or tumor intestinal mucosa tissues of Apc (Min/+)/Spint1 (flox/flox)/Vil-Cre mice were analysed. The experiment was repeated respectively.
2013-04-01 | E-GEOD-40856 | biostudies-arrayexpress
Project description:Aberrant DNA methylation is frequent in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are poorly understood. Ten-Eleven Translocation (TET) dioxygenases and Thymine DNA Glycosylase (TDG) mediate active DNA demethylation by generating and removing oxidized cytosine species. TET1 and TDG mutations, and altered levels of oxidized cytosines have been identified in human CRC. To investigate the TET-TDG demethylation axis in intestinal tumorigenesis, we generated ApcMin mice that are devoid of Tet1 and/or Tdg, and characterized the methylome and transcriptome of intestinal adenomas. There were increased numbers (>30) of adenomas in ApcMin mice expressing the dominant-negative TdgN151A allele, whereas Tet1-deficient and Tet1/Tdg-double heterozygous ApcMin adenomas were larger and displayed features of erosion and invasion. Methylome analysis revealed reduction in global DNA hypomethylation in colonic adenomas from Tet1- and Tdg-mutant ApcMin mice, and hypermethylation of CpG islands in Tet1-mutant ApcMin mice. In addition, RNA sequencing showed upregulation of inflammatory, immune and interferon response genes in Tet1- and Tdg-mutant colonic adenomas compared to control ApcMin adenomas. The corresponding 127-gene inflammatory signature separated human colonic adenocarcinomas in four groups, closely aligned with their microsatellite or chromosomal instability, and characterized by different levels of DNA methylation and DNMT1 expression that anti-correlated with TET1 expression. These findings demonstrate a novel mechanism of epigenetic regulation during intestinal tumorigenesis by which TET1-TDG-mediated DNA demethylation may decrease methylation levels and inflammatory/interferon/immune responses, and is linked to the type of genomic instability.
2024-07-01 | GSE179313 | GEO
Project description:Aberrant DNA methylation is frequently observed in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are poorly understood. Ten-Eleven Translocation (TET) dioxygenases and Thymine DNA Glycosylase (TDG) are involved in active DNA demethylation by generating and removing novel oxidized cytosine species. TET1 and TDG mutations, and alterations of the levels of oxidized cytosines have been identified in human CRC. To clarify the biological significance of the TET-TDG demethylation axis in intestinal tumorigenesis, we generated ApcMin mice that are devoid of Tet1 and/or Tdg, and characterized the methylome and transcriptome of intestinal adenomas by DREAM and RNA sequencing, respectively. Tet1-deficient and Tet1/Tdg-double heterozygous ApcMin adenomas manifested increased adenoma size and features of erosion or invasion, whereas an increased number (>30) of adenomas was found in Tdg-mutant ApcMin mice. Methylome analysis revealed progressive loss of global DNA hypomethylation in colonic adenomas from Tet1- and Tdg-deficient ApcMin mice, and hypermethylation of CpG islands in Tet1-deficient ApcMin mice. In addition, RNA sequencing showed upregulation of genes in inflammatory, immune and interferon response in Tet1- and Tdg-mutant colonic adenomas compared to control ApcMin adenomas. The corresponding 135-gene inflammatory signature separated human colonic adenocarcinomas into four groups, closely aligned with their microsatellite or chromosomal instability profile, and characterized by different levels of DNA methylation and DNMT1 expression levels that anti-correlated with TET1 expression levels. These findings demonstrate a novel mechanism of epigenetic regulation during intestinal tumorigenesis by which TET1-TDG-mediated active DNA demethylation decreases not only methylation levels, but also inflammatory/interferon/immune response, which impinges on the intrinsic features of genomic instability of the tumors. This study establishes a novel link, via inflammatory response, between epigenomic and genomic instability.
2023-10-01 | GSE179526 | GEO
Project description:Analysis of metabolic pathway gene expression. The hypothesis tested in the present study is to assess mRNA level changes in metabolic genes in intestinal tumors from APCmin mice overexpressing PGC-1β specifically in the intestine. Total RNA obtained from ileum tumor samples from iPGC-1β/APCmin mice was compared to the total RNA extracted from FVBN/APCmin mice.
2015-03-01 | E-GEOD-61642 | biostudies-arrayexpress
Project description:Osteopontin (OPN) is a secreted phosphoglycoprotein, and is a transcriptional target of aberrant Wnt signaling. OPN is upregulated in human colon cancers, and is suggested to enhance cancer progression. In this study, the effect of deficiency of OPN on intestinal tumor development in Apc-deficient Min mice was investigated. At 16 weeks of age, the number of small intestinal polyps in Min/OPN(+/-) and Min/OPN(-/-) mice was lower than that of Min/OPN(+/+) mice. Colorectal tumor incidences and multiplicities in Min/OPN(+/-) and Min/OPN(-/-) mice were significantly lower than those in Min/OPN(+/+) mice, being 48% and 0.6 ± 0.8, 50% and 0.8 ± 0.9 vs. 80% and 1.6 ± 1.7, respectively. OPN expression in colorectal tumors was strongly upregulated in Min/OPN(+/+) compared to adjacent non-tumor parts, but was decreased in Min/OPN(+/-) and not detected in Min/OPN(-/-). Targets of OPN, matrix metalloproteinases (MMPs)-3, -9, and -13 were lowered by OPN deficiency. Macrophage marker F4/80 in colorectal tumors was also lowered by OPN deficiency. MMP-9 expression was observed in tumor cells and tumor-infiltrating neutrophils. These results indicate that induction of OPN by aberrant Wnt signaling could enhance colorectal tumor development in part by upregulation of MMP-3, -9, and -13 and infiltration of macrophage and neutrophils. Suppression of OPN expression could contribute to tumor prevention, but complete deficiency of OPN may cause some adverse effects.
| S-EPMC5454970 | biostudies-literature
Project description:Transcriptional Profiling of the Transition from Normal Intestine to Adenoma in the APC(Min/+) Mouse. Tissue was from male 91-days old APC(Min/+) mouse (an animal model for human colon cancer). RNA was purified using Trizol and labeled for hybridization to high density oligonucleotide Affymetrix MG_U74Av2 arrays, using manufacturer protocol. We measured the relative expression level of >12000 genes and ESTs. ----------------------------------------- Samples used in analysis: * GSM12501: Normal intestine diet #1 sample C1_0112 Dnmt+/- Min/+ * GSM12502: Tumor diet #1 sample T1_0112 Dnmt+/- Min/+ * GSM12503: Normal intestine diet #1 sample C2_0112 Dnmt+/+ Min/+ * GSM12504: Tumor diet #1 sample T2_0112 Dnmt+/+ Min/+ * GSM12505: Normal intestine diet #2 sample C1_003 Dnmt+/- Min/+ * GSM12506: Tumor diet #2 sample T1_003 Dnmt+/- Min/+ * GSM12507: Normal intestine diet #2 sample C2_003 Dnmt+/+ Min/+ * GSM12508: Tumor diet #2 sample T2_003 Dnmt+/+ Min/+ * GSM12509: Normal intestine diet #3 sample C1_005 Dnmt+/- Min/+ * GSM12510: Tumor diet #3 sample T1_005 Dnmt+/- Min/+ * GSM12511: Normal intestine diet #3 sample C2_005 Dnmt+/+ Min/+ * GSM12512: Tumor diet #3 sample T2_005 Dnmt+/+ Min/+ - - - - - - - - - - - - - - - - - - - - - Comparisons were performed as described in Chen Z, Ge B, Hudson TJ and Rozen R. Gene Expression Patterns 1, 89-93, 2002. Comparing Normal intestine vs Adenoma. - - - - - - - - - - - - - - - - - - - - - This resulted in the identification of differentially expressed transcripts. Identified transcripts were clustered based on functional information which was publicly available at time of analysis, obtained through the NetAffx WEB portal (www.Affymetrix.com) and literature. Keywords = Mouse Keywords = Min Keywords = normal Keywords = intestine Keywords = tumor Keywords = tumour Keywords = colon cancer Keywords = gene expression Keywords = beta-catenin Keywords = high density oligonucleotide microarrays Keywords = familial adenomatous polyposis Keywords = FAP Keywords = colorectal cancer Keywords = Affymetrix MGU74Av2 GeneChip probe array Keywords = mouse model Keywords = APC Keywords = adenomatous polyposis coli Keywords: ordered
2004-10-18 | GSE784 | GEO
Project description:Nearly all colorectal cancers have dysregulated Wnt signalling, predominantly through the mutation of the Apc (Adenomatous Polyposis Coli) gene. Therefore it is of vital importance to elucidate the key Wnt target genes in intestinal cells in vivo. We have used a novel inducible cre-lox based murine system (designated ApcFlox) to investigate the consequences of perturbation of Wnt signalling following inactivation of Apc in vivo within 100% of the intestinal epithelium. We have employed microarray analysis at 3 time points within our ApcFlox system (Day 3 prior to the onset of phenotype, day 4 the establishment of the phenotype and day 5 gross phenotype of altered proliferation, differentiation and migration) and from adenomas arising in the ApcMin/+ background allowing us characterise Wnt/beta-catenin target genes based on their expression profiles during different stages of intestinal tumourigenesis. Furthermore, we have employed microarray analysis using livers from our ApcFlox system and have demonstrated that there is very little overlap in the Wnt target genes induced by Apc loss in the liver and the intestine. More importantly, we have been able to determine a novel set of putative Wnt/beta-catenin target genes which are upregulated at both early and late stages of tumourigenesis in the intestine and may represent novel therapeutic targets in colon cancer. Samples were collected from Genetcially modified mice of the genotypes indicated on the sample records. Where appropriate, gene recombination was induced using IP administration of beta-napthoflavone. Cohorts of samples were used to compare the affects of APC loss in the small intestine at three time points (and compared to matched control samples in which the gene was not recombined). Furthermore, these samples were compared to colonic polyps (and normal colon) taken from the Apcmin Mouse.
2015-01-31 | E-GEOD-65461 | biostudies-arrayexpress
Project description:Tumors consist of a heterogeneous population of neoplastic cells infiltrated by an equally heterogeneous collection of nonneoplastic cells that comprise the tumor microenvironment. Tumor growth, invasion, and metastasis depend on multiple interactions between these cells. To assess their potential as therapeutic targets or vehicles for tumor specific delivery of therapeutic agents, we examined the contribution of bone marrow derived cells (BMDCs) to the intestinal tumor microenvironment. Hematopoietic stem cells expressing the enhanced green fluorescent protein (eGFP) were transplanted into lethally irradiated ApcMin/+ mice, and their engraftment was analyzed by confocal microscopy. The results showed abundant infiltration of eGFP cells into the small intestine, colon, and spleen compared to heart, muscle, liver, lung, and kidney. Within the intestine, there was a pronounced gradient of engraftment along the anterior to posterior axis, with enhanced infiltration into adenomas. Immunofluorescence analysis showed that osteopontin was expressed in tumor stromal cells but not in nontumor stromal populations, suggesting that gene expression in these cells is distinct. Tumor vasculature in ApcMin/+ mice was chaotic compared to normal intestinal regions. Our data suggest that BMDCs can be harnessed for tumor-targeted therapies to enhance antitumor efficacy.
| S-EPMC3362927 | biostudies-literature
Project description:Transcriptional Profiling of the Transition from Normal Intestine to Adenoma in the APC(Min/+) Mouse. Tissue was from male 91-days old APC(Min/+) mouse (an animal model for human colon cancer). RNA was purified using Trizol and labeled for hybridization to high density oligonucleotide Affymetrix MG_U74Av2 arrays, using manufacturer protocol. We measured the relative expression level of >12000 genes and ESTs. -----------------------------------------; Samples used in analysis:; * GSM12501: Normal intestine diet #1 sample C1_0112 Dnmt+/- Min/+; * GSM12502: Tumor diet #1 sample T1_0112 Dnmt+/- Min/+; * GSM12503: Normal intestine diet #1 sample C2_0112 Dnmt+/+ Min/+; * GSM12504: Tumor diet #1 sample T2_0112 Dnmt+/+ Min/+; * GSM12505: Normal intestine diet #2 sample C1_003 Dnmt+/- Min/+; * GSM12506: Tumor diet #2 sample T1_003 Dnmt+/- Min/+; * GSM12507: Normal intestine diet #2 sample C2_003 Dnmt+/+ Min/+; * GSM12508: Tumor diet #2 sample T2_003 Dnmt+/+ Min/+; * GSM12509: Normal intestine diet #3 sample C1_005 Dnmt+/- Min/+; * GSM12510: Tumor diet #3 sample T1_005 Dnmt+/- Min/+; * GSM12511: Normal intestine diet #3 sample C2_005 Dnmt+/+ Min/+; * GSM12512: Tumor diet #3 sample T2_005 Dnmt+/+ Min/+; - - - - - - - - - - - - - - - - - - - - -; Comparisons were performed as described in Chen Z, Ge B, Hudson TJ and Rozen R. Gene Expression Patterns 1, 89-93, 2002. Comparing Normal intestine vs Adenoma. - - - - - - - - - - - - - - - - - - - - -; This resulted in the identification of differentially expressed transcripts. Identified transcripts were clustered based on functional information which was publicly available at time of analysis, obtained through the NetAffx WEB portal (www.Affymetrix.com) and literature.
2008-06-15 | E-GEOD-784 | biostudies-arrayexpress
Project description:Comparison of Villin-Cre;Apc min;Lef1 fl/fl (VApcMinL) and ApcMin adenoma cells at the age of 11 wks. 2-3 male mice and 3-10 tumors per group were used in the experiment. Experiment was repeated twice (ApcMin2 and VApcMinL2 samples).
2021-12-10 | GSE174097 | GEO