Transcription profiling by array of small intestinal and colonic hyperplastic crypt compartment upon Apc depletion
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Michal Kolar
PROVIDER: E-MTAB-6915 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The first step in the development of human colorectal cancer (CRC) is the aberrant hyperactivation of the Wnt signaling pathway, predominantly caused by inactivating mutations in the adenomatous polyposis coli (APC) gene which encodes an essential tumor suppressor. In order to identify genes affected by Apc loss, expression profiling of intestinal epithelium isolated from mice harboring the conditional allele of the gene was performed. The gene encoding transcriptional factor msh homeobox 1 (Msx1) displayed robust upregulation upon Apc inactivation. To characterize the gene signature in colon upon Msx1 depletion, colonic epithelium from mice harboring conditional alleles of Apc and Msx1 was isolated and the gene expression profile was compared with control mice harboring the conditional allele of Apc only.
2019-11-01 | E-MTAB-6909 | biostudies-arrayexpress
Project description:The first step in the development of human colorectal cancer is the aberrant hyperactivation of the Wnt signaling pathway, predominantly caused by inactivating mutations in the adenomatous polyposis coli (Apc) gene encoding an essential tumor suppressor. The gene encoding transcriptional factor msh homeobox 1 (Msx1) displayed robust upregulation upon Apc inactivation in intestinal epithelium isolated in mice harboring the conditional allele of the Apc gene. To identify the gene signature in the small intestine upon Msx1 depletion, small intestinal epithelium from mice harboring conditional alleles of Apc and Msx1 was isolated and the gene expression profile was compared with control mice harboring the conditional allele of Apc only.
2019-11-01 | E-MTAB-6930 | biostudies-arrayexpress
Project description:Tumor Associated Calcium Signal Transducer 2 (TACSTD2) is one of the cancer-related genes whose overexpression correlates with tumor progression and invasiveness in human colorectal cancer. TACSTD2 gene encodes for a transmembrane glycoprotein TROP2, which is implicated in altered expression of epithelial-mesenchymal transition (EMT) markers and may play a role in metastasis formation. To monitor the onset of TROP2 in hyperplastic cells and its effect on aberrant signaling potentially leading to tumor growth, we isolated epithelial cells from the mouse small intestine 7 days after disruption of the Adenomatous polyposis coli (Apc) gene. Loss of APC tumor suppressor function is the most common initial step in the development of colon cancer in humans. In the mice, the epithelial hyperproliferation occurs within a few days after Apc disruption, accompanied by the formation of ectopic crypts, followed by the formation of microadenomas over time. We performed expression profiling of Trop2+ and Trop2- hyperproliferating cells and, in addition, non-proliferating cells of the intestinal epithelium, including predominantly differentiated cells.
2022-11-29 | E-MTAB-11377 | biostudies-arrayexpress
Project description:The first step in the development of human colorectal cancer (CRC) is the aberrant hyperactivation of the Wnt signaling pathway, predominantly caused by inactivating mutations in the adenomatous polyposis coli (APC) gene encoding an essential tumor suppressor. In order to identify genes affected by Apc loss, expression profiling of intestinal epithelium isolated from mice harboring the conditional allele of the gene was performed. The gene encoding transcriptional factor msh homeobox 1 (Msx1) displayed robust upregulation upon Apc inactivation. Subsequently, the expression pattern of human MSX1 was examined in a collection of colonic tumors. The MSX1 mRNA level was increased in all types of human intestinal neoplasia tested. In order to identify genes affected by MSX1 loss, expression profiling of human colorectal cancer cells SW620 upon MSX1 gene depletion was performed.
2019-11-01 | E-MTAB-6928 | biostudies-arrayexpress
Project description:Tumor Associated Calcium Signal Transducer 2 (TACSTD2) is one of the cancer-related genes whose overexpression correlates with tumor progression and invasiveness in human colorectal cancer. TACSTD2 gene encodes for a transmembrane glycoprotein TROP2, which is implicated in altered expression of epithelial-mesenchymal transition (EMT) markers and may play a role in metastasis formation. To determine how TROP2 affects aberrant tumor cell signaling, we isolated early adenoma cells from the mouse small intestine 6 weeks after disruption of the Adenomatous polyposis coli (Apc) gene, one of the first steps in the development of colorectal cancer in human. We performed expression profiling of Trop2+ and Trop2- tumor cells and, in addition, non-tumor cells of the intestinal epithelium, including predominantly differentiated cells.
2022-11-29 | E-MTAB-11382 | biostudies-arrayexpress
Project description:Oncogenic mutations that drive colorectal cancer can be present in healthy intestines for long periods without overt consequence. Mutation of Adenomatous polyposis coli (Apc), the most common initiating event in conventional adenomas, activates Wnt signaling, hence conferring fitness on mutant intestinal stem cells (ISCs). Apc mutations may occur in ISCs that arose by routine self-renewal or by dedifferentiation of their progeny. Although ISCs of these different origins are fundamentally similar, it is unclear if both generate tumours equally well in uninjured intestines. Also unknown is whether cis-regulatory elements are substantively modulated upon Wnt hyperactivation or as a feature of subsequent tumours. Here, we show in two mouse models that adenomas are not an obligatory outcome of Apc deletion in either ISC source but require proximity of mutant intestinal crypts. Reduced crypt density abrogates, and aggregation of mutant colonic crypts augments, adenoma formation. Moreover, adenoma-resident ISCs open chromatin at thousands of enhancers that are inaccessible in Apc-null ISCs not associated with adenomas. These cis-elements explain adenoma-selective gene activity and persist, with little further expansion of the repertoire, as other oncogenic mutations accumulate. Thus, cooperativity between neighbouring mutant crypts and new accessibility at specific enhancers are key steps early in intestinal tumourigenesis.
2024-11-15 | GSE241380 | GEO
Project description:Oncogenic mutations that drive colorectal cancer can be present in healthy intestines for long periods without overt consequence. Mutation of Adenomatous polyposis coli (Apc), the most common initiating event in conventional adenomas, activates Wnt signaling, hence conferring fitness on mutant intestinal stem cells (ISCs). Apc mutations may occur in ISCs that arose by routine self-renewal or by dedifferentiation of their progeny. Although ISCs of these different origins are fundamentally similar, it is unclear if both generate tumours equally well in uninjured intestines. Also unknown is whether cis-regulatory elements are substantively modulated upon Wnt hyperactivation or as a feature of subsequent tumours. Here, we show in two mouse models that adenomas are not an obligatory outcome of Apc deletion in either ISC source but require proximity of mutant intestinal crypts. Reduced crypt density abrogates, and aggregation of mutant colonic crypts augments, adenoma formation. Moreover, adenoma-resident ISCs open chromatin at thousands of enhancers that are inaccessible in Apc-null ISCs not associated with adenomas. These cis-elements explain adenoma-selective gene activity and persist, with little further expansion of the repertoire, as other oncogenic mutations accumulate. Thus, cooperativity between neighbouring mutant crypts and new accessibility at specific enhancers are key steps early in intestinal tumourigenesis.
2024-11-10 | GSE281056 | GEO
Project description:The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated in the vast majority of human colorectal cancers (CRC) and leads to deregulated Wnt signaling. To determine whether Apc disruption is required for tumor maintenance, we developed a mouse model of CRC whereby Apc can be conditionally suppressed using a doxycycline-regulated shRNA. Apc suppression produces adenomas in both the small intestine and colon that, in the presence of Kras and p53 mutations, can progress to invasive carcinoma. In established tumors, Apc restoration drives rapid and widespread tumor-cell differentiation and sustained regression without relapse. Tumor regression is accompanied by the re-establishment of normal crypt-villus homeostasis, such that once aberrantly proliferating cells reacquire self-renewal and multi-lineage differentiation capability. Our study reveals that CRC cells can revert to functioning normal cells given appropriate signals, and provide compelling in vivo validation of the Wnt pathway as a therapeutic target for treatment of CRC Analysis of RNA isolated from colon polyps that presented in shAPC or shAPC/Kras mice as compared to shRenilla (neutral) mouse colon mucosa
2015-06-18 | E-GEOD-67186 | biostudies-arrayexpress
Project description:Oncogenic mutations that drive colorectal cancer can be present in healthy intestines for long periods without overt consequence. Mutation of Adenomatous polyposis coli (Apc), the most common initiating event in conventional adenomas, activates Wnt signaling, hence conferring fitness on mutant intestinal stem cells (ISCs). Apc mutations may occur in ISCs that arose by routine self-renewal or by dedifferentiation of their progeny. Although ISCs of these different origins are fundamentally similar, it is unclear if both generate tumours equally well in uninjured intestines. Also unknown is whether cis-regulatory elements are substantively modulated upon Wnt hyperactivation or as a feature of subsequent tumours. Here, we show in two mouse models that adenomas are not an obligatory outcome of Apc deletion in either ISC source but require proximity of mutant intestinal crypts. Reduced crypt density abrogates, and aggregation of mutant colonic crypts augments, adenoma formation. Moreover, adenoma-resident ISCs open chromatin at thousands of enhancers that are inaccessible in Apc-null ISCs not associated with adenomas. These cis-elements explain adenoma-selective gene activity and persist, with little further expansion of the repertoire, as other oncogenic mutations accumulate. Thus, cooperativity between neighbouring mutant crypts and new accessibility at specific enhancers are key steps early in intestinal tumourigenesis.
2024-11-15 | GSE241383 | GEO
Project description:Oncogenic mutations that drive colorectal cancer can be present in healthy intestines for long periods without overt consequence. Mutation of Adenomatous polyposis coli (Apc), the most common initiating event in conventional adenomas, activates Wnt signaling, hence conferring fitness on mutant intestinal stem cells (ISCs). Apc mutations may occur in ISCs that arose by routine self-renewal or by dedifferentiation of their progeny. Although ISCs of these different origins are fundamentally similar, it is unclear if both generate tumours equally well in uninjured intestines. Also unknown is whether cis-regulatory elements are substantively modulated upon Wnt hyperactivation or as a feature of subsequent tumours. Here, we show in two mouse models that adenomas are not an obligatory outcome of Apc deletion in either ISC source but require proximity of mutant intestinal crypts. Reduced crypt density abrogates, and aggregation of mutant colonic crypts augments, adenoma formation. Moreover, adenoma-resident ISCs open chromatin at thousands of enhancers that are inaccessible in Apc-null ISCs not associated with adenomas. These cis-elements explain adenoma-selective gene activity and persist, with little further expansion of the repertoire, as other oncogenic mutations accumulate. Thus, cooperativity between neighbouring mutant crypts and new accessibility at specific enhancers are key steps early in intestinal tumourigenesis.
2024-11-15 | GSE241382 | GEO