Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA227435 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In this experiment the RNA of s.c. grown tumors of cancer cell lines of murine Ptf1aCre;Kras,Brg1-/- vs. Ptf1a;Kras;p53+/- PDA was isolated and analyzed for gene expression. Ptf1aCre;Kras,Brg1-/- s.c. PDA grows more benign as compared to Ptf1a;Kras;p53+/- PDA; and the rationale of this study was to identify genes responsible for this different biological behavior. Total RNA of s.c. tumors of Ptf1aCre;Kras,Brg1-/- vs. Ptf1a;Kras;p53+/- cancer cell lines was isolated, purified and analyzed on the deep sequencing platform.
2013-11-14 | E-GEOD-52332 | biostudies-arrayexpress
Project description:In this experiment the RNA of s.c. grown tumors of cancer cell lines of murine Ptf1aCre;Kras,Brg1-/- vs. Ptf1a;Kras;p53+/- PDA was isolated and analyzed for gene expression. Ptf1aCre;Kras,Brg1-/- s.c. PDA grows more benign as compared to Ptf1a;Kras;p53+/- PDA; and the rationale of this study was to identify genes responsible for this different biological behavior.
2013-11-14 | GSE52332 | GEO
Project description:Mutations of subunit genes of the SWI/SNF chromatin remodeling complexes were found in 12-23% of human Pancreatic Ductal Adenocarcinoma (PDAC). We previously showed that Brg1, a catalytic ATPase subunit of the SWI/SNF chromatin remodeling complexes, inhibits the formation of intraductal pancreatic mucinous neoplasms (IPMN) and IPMN-derived PDAC from ductal cells. On the other hand, ARID1A is the most frequent target of mutations in the SWI/SNF chromatin remodeling complexes in human PDAC. We found that Arid1a loss in the context of mutant Kras resulted in formation of IPMN and PDAC. We also found that the incidence of PDAC formation in Ptf1a-Cre; KrasG12D; Arid1af/f mice was markedly lower than that in Ptf1a-Cre; KrasG12D; Brg1f/f mice despite the similarities between Arid1a-deficient and Brg1-deficient IPMNs. We extracted total RNA from intraductal papillary mucinous neoplasms (IPMNs) in Ptf1a-Cre; KrasG12D; Arid1af/f and Ptf1a-Cre; KrasG12D; Brg1f/f mice and perform microarray analysis.
2018-03-31 | GSE96926 | GEO
Project description:The fundamental biology of pancreatic ductal adenocarcinoma has been greatly impacted by the characterization of genetically engineered mouse models that allow temporal and spatial activation of oncogenic KRAS (KRASG12D). One of the most commonly used models involves targeted insertion of a cre-recombinase into the Ptf1a gene. However, this approach disrupts the Ptf1a gene, resulting in haploinsufficiency that likely affects sensitivity to oncogenic KRAS (KRASG12D). This study aims to determine if Ptf1a haploinsufficiency affected the acinar cell response to KRASG12D before and after induction of pancreatic injury. Taken together, our results suggest Ptf1a haploinsufficiency in Ptf1acreERT mouse models promotes KRASG12D priming of genes for promotion of PDAC.
2024-08-20 | GSE252884 | GEO
Project description:Brahma related gene 1 (BRG1), a catalytic ATPase subunit of SWI/SNF chromatin remodeling complexes, is silenced in approximately 10% of human pancreatic ductal adenocarcinomas (PDA). We previously showed that BRG1 inhibits the formation of intraductal pancreatic mucinous neoplasm (IPMN) and IPMN-derived PDA from ductal cells. However, the role of BRG1 in pancreatic intraepithelial neoplasia (PanIN) from acinar cells remains elusive. Here, we investigated the role of BRG1 in PanIN initiation and maintenance and its underlying mechanisms. Exclusive elimination of Brg1 in acinar cells of Ptf1a-CreER; KrasG12D; Brg1f/f (KBC) mice impaired the formation of acinar-to-ductal metaplasia (ADM) and PanIN independent of the presence of p53 mutation. We found that Sox9 expression was down-regulated in both Brg1-depleted acinar cell explants and BRG1-depleted ADMs/PanINs. Sox9 overexpression rescued this PanIN-attenuated phenotype in KBC mice. Furthermore, Brg1-deletion in established PanIN by using an inducible dual recombinase system resulted in regression of the lesions in mice. Finally, expression of BRG1 and SOX9 was also positively correlated in human PanIN-derived PDAs. In summary, BRG1 is critical for both initiation and maintenance of PanIN. Mechanistically, this is mediated through positive regulation of SOX9 expression. Thus, the BRG1/SOX9 axis is a potential target for the prevention of PanIN-derived PDA.
2018-01-01 | GSE93615 | GEO
Project description:We have carried out transcriptional profile analysis in WT MICE and bitransgenic Pdx1-cre/Kras*A MICE baring Pancreatic Ductal Adenocarcinoma Mouse models faithfully simulating human cancer are valuable for genetic identification of potential drug-targets but, among them, the most advantageous for practical use in subsequent preclinical testing of candidate therapeutic regimes are those exhibiting rapid tumor development. Considering that a KRAS mutation (predominantly in codon 12, such as KRASG12D; KRAS*) occurs with high frequency (~90%) in cases of human pancreatic ductal adenocarcinoma (PDA)1, we sought to develop a mouse PDA model that would exhibit high tumor incidence and short latency by ectopic overexpression of Kras*. Five WT mice and 6 bitransgenic Pdx1-cre/Kras*A MICE baring Pancreatic Ductal Adenocarcinoma were used to identify key genes in the formation of panceatic malignacies
2014-09-01 | E-GEOD-53659 | biostudies-arrayexpress
Project description:Brg1 is a subunit of SWI/SNF chromatin remodeling complex. To clarify the role of Brg1 for the progression and metastasis of pancreatic ductal adenocarcinoma (PDAC), we generated a PDAC mouse model with a dual recombinase system (Brg1 lox/lox; Pdx1-Flp; Kras FSF-G12D; Trp53 frt/frt; Rosa26 FSF-CreERT2) which enabled to ablate Brg1 in established PDAC with tamoxifen treatment. We established cancer cell lines derived from PDAC tumors developed in those mice and investigated the effect of Brg1 ablation on PDAC cell proliferation and metastasis. In order to determine the genes expression in Brg1-deleted mouse PDAC cells, we conducted a transcriptomic analysis using microarray using Brg1 wild type and Brg1-deleted mouse PDAC cells.
2022-04-30 | GSE199442 | GEO
Project description:Constitutive Kras and NF-kB activation is identified as signature alterations in human pancreatic ductal adenocarcinoma (PDAC). Here, we report that pancreas-targeted IKK2/beta inactivation inhibited NF-kB activation and completely suppressed PDAC development. Our findings demonstrated that NF-kB is required for development of pancreatic ductal adenocarcinoma that was initiated by Kras activation.
2012-01-24 | GSE33322 | GEO
Project description:Pancreatic Ductal Adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a “ductal like” state during PanIN-PDA formation. Here, we demonstrate a parallel mechanism operative in mature duct cells where they undergo “ductal retrogression” to form IPMN-PDA. Brg1, a catalytic subunit of the SWI/SNF complexes, plays a critical antagonistic role in IPMN-PDA development. In mature duct cells Brg1 inhibits the dedifferentiation that precedes neoplastic transformation, thus attenuating tumor initiation. In contrast, Brg1 promotes tumorigenesis in full-blown PDA by supporting a mesenchymal-like transcriptional landscape. We have exploited this duality of Brg1 functions to develop a novel therapeutic approach using an epigenetic drug JQ1. In summary, this study demonstrates the context-dependent roles of Brg1 and points to potential therapeutic treatment options based on epigenetic regulation in PDA. Duct cells were isolated from mice of 3 different genotypes and duct cells from 3 mice of each genotype were sequenced. For the put back experiments, control retrovirus and that expressing Brg1 were transdcued in Brg1 null IPMN mouse cell line.
2015-07-29 | E-GEOD-65315 | biostudies-arrayexpress
Project description:Background & Aims Intraductal tubulopapillary neoplasm (ITPN) is a rare, high-grade tumour of the pancreatic duct, characterised by distinct molecular features including frequent alterations in the components of switch/sucrose non-fermenting (SWI/SNF) chromatin remodelling complex and PI3K/AKT pathways. This study aimed to investigate the functional role of BRG1, a key SWI/SNF component, in pancreatic ductal cells, particularly in the context of PI3K/AKT pathway activation. Methods We generated conditional knockout mice by crossing Hnf1b-CreERT2, Brg1flox, and Ptenflox strains. Pancreatic organoids were used for subcutaneous xenografts in NOD/SCID mice. Twelve human ITPN specimens were analysed by immunohistochemistry. Results: In the context of PI3K/AKT pathway activation, Brg1 deletion in pancreatic ductal cells led to the development of ITPN accompanied by invasive carcinoma components. An upregulation of the Yes-associated protein 1/transcriptional coactivator with the PDZ-binding motif (YAP/TAZ) pathway was observed in mutant pancreatic ductal cells. In the xenograft model, pancreatic tumour organoids progressed into invasive pancreatic ductal adenocarcinoma (PDAC) with high TAZ expression, indicating sustained YAP/TAZ pathway activation. Furthermore, administration of verteporfin, a YAP/TAZ pathway inhibitor, reduced tumour formation and partially reversed the dedifferentiation of pancreatic ductal cells. Consistent with the mouse data, analysis of 12 human ITPN specimens showed frequent downregulation of SWI/SNF components, with a significant inverse correlation between BRG1 and TAZ expression. Conclusions: Simultaneous loss of Brg1 and Pten in pancreatic ductal cells results in ITPN formation via the activation of the YAP/TAZ pathway in the mose model. The YAP/TAZ pathway is a key driver of ITPN formation and is a potential therapeutic target for ITPN and ITPN-derived PDAC.
2025-10-13 | GSE304938 | GEO