Transcriptional profiling of Liver tissue from mice with bcatenin and Myc mutations
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE230137 | GEO | 2023/04/28
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression was profiled in different regions of mouse liver with either Bcatenin exon3 mutation or Bcatenin exon3/Myc mutation at the noted time points.
2023-04-28 | GSE230644 | GEO
Project description:Gene expression changes were examined in transgenic MYC-driven liver cancers at different time points as tumors formed and upon early regression. Time points evaluated include: Control (non-tumor bearing), Pre-tumor (mice were removed from doxyclycine in their diet to induce MYC oncogene expression for 4-5 weeks), Tumor (tumor nodules from mice that had been off of doxycycline for 8-9 weeks) and Early tumor regression (tumor-bearing mice were placed back on doxycycline for 72 hrs to inhibit MYC oncogene expresion). MYC-Driven Mouse Tumor Models are described in Schahaf, et al., Nature, 2004 and Goga, et al., Nature Medicine, 2007.
2011-07-06 | GSE28198 | GEO
Project description:A profile of gene expression differences in mouse small intestine with short term induction of Apc inactivation, in the presence and absence of additional mutations in combinations of Kras, Pik3ca, Pten, and Slc7a5.
2024-07-19 | GSE272639 | GEO
Project description:Gene expression changes were examined in transgenic MYC-driven liver cancers at different time points as tumors formed and upon early regression. Time points evaluated include: Control (non-tumor bearing), Pre-tumor (mice were removed from doxyclycine in their diet to induce MYC oncogene expression for 4-5 weeks), Tumor (tumor nodules from mice that had been off of doxycycline for 8-9 weeks) and Early tumor regression (tumor-bearing mice were placed back on doxycycline for 72 hrs to inhibit MYC oncogene expresion). MYC-Driven Mouse Tumor Models are described in Schahaf, et al., Nature, 2004 and Goga, et al., Nature Medicine, 2007. 11 Total Samples: 3 Control, 4 Pre-Tumor, 4 Tumor, 4 Early Tumor Regression. Control = LAP-tTA transgenic mice. Others = TRE-MYC x LAP-tTA double transgenic mice (doxy off).
2011-07-06 | E-GEOD-28198 | biostudies-arrayexpress
Project description:Dysregulated Wnt signalling is seen in approximately 30% of hepatocellular cancers, thus finding pathways downstream of activation of Wnt signalling is key. Using cre lox technology we have deleted the the adenomatous polyposis coli tumour suppressor protein (Apc) within the adult mouse liver and observed a rapid increase in nuclear beta-catenin and C-Myc. This is associated with an induction of proliferation leading to hepatomegally within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes we analysed the impact of inactivating Apc in the context of deficiency of the potentially key effectors beta-catenin and c-Myc. beta-catenin loss rescues both the proliferation and hepatomegally phenotypes following Apc loss. However c-Myc deletion, which rescues the phenotypes of Apc loss in the intestine, had no effect on the phenotypes of Apc loss. The consequences of deregulation the Wnt pathway within the liver are therefore strikingly different to those observed within the intestine, with the vast majority of Wnt targets beta-catenin dependent but c-Myc independent in the liver. Samples were collected from Genetcially modified mice of the genotypes indicated in the characteristics field. Gene recombination was induced using IP administration of beta-napthoflavone. Cohorts of samples were used to compare the affects of APC loss, cMYC loss and combined APC and cMYC loss in the liver (and compared to matched control samples in which the genes were not recombined).
2015-01-31 | E-GEOD-65476 | biostudies-arrayexpress
Project description:Dysregulated Wnt signalling is seen in approximately 30% of hepatocellular cancers, thus finding pathways downstream of activation of Wnt signalling is key. Using cre lox technology we have deleted the the adenomatous polyposis coli tumour suppressor protein (Apc) within the adult mouse liver and observed a rapid increase in nuclear beta-catenin and C-Myc. This is associated with an induction of proliferation leading to hepatomegally within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes we analysed the impact of inactivating Apc in the context of deficiency of the potentially key effectors beta-catenin and c-Myc. beta-catenin loss rescues both the proliferation and hepatomegally phenotypes following Apc loss. However c-Myc deletion, which rescues the phenotypes of Apc loss in the intestine, had no effect on the phenotypes of Apc loss. The consequences of deregulation the Wnt pathway within the liver are therefore strikingly different to those observed within the intestine, with the vast majority of Wnt targets beta-catenin dependent but c-Myc independent in the liver.
2015-01-31 | GSE65476 | GEO
Project description:The effect of EZH2 inhibitor DZNeP on the small intestine of mice deificient in Apc was examined with RNAseq.
2023-04-30 | GSE229639 | GEO
Project description:Here we report a dosage effect of c-Myc on hematopoiesis and its distinct role in mediating the Wnt/b-catenin pathway in hematopoietic stem cell (HSC) and bone marrow niche cells. We showed that c-Myc haploinsufficiency led to ineffective hematopoiesis by inhibiting HSC self-renewal and quiescence, and promoting its apoptosis. We have identified Nr4a1, Nr4a2 and Jmjd3, which are critical for the maintenance of HSC functions, as previously unrecognized downstream targets of c-Myc in HSCs. c-Myc directly binds to the promoter regions of Nr4a1, Nr4a2 and Jmjd3 and regulates their expression. Our results revealed that Nr4a1 and Nr4a2 mediated the function of c-Myc in regulating HSC quiescence while all three genes contribute to the function of c-Myc in the maintenance of HSC survival. Adenomatous polyposis coli (Apc) is a negative regulator of the Wnt/b-catenin pathway. We have provided the first evidence that Apc haploinsufficiency induced a blockage of erythroid lineage differentiation through promoting expression and secretion of IL6 in bone marrow endothelial cells. We found that c-Myc haploinsufficiency failed to rescue defective function of Apc-deficient HSCs in vivo but it was sufficient to prevent the development of severe anemia in Apc heterozygous mice, and to significantly prolong survival of such mice. Furthermore, we showed that c-Myc mediated Apc loss-induced IL6 secretion in endothelial cells, and c-Myc haploinsufficiency reversed the negative effect of Apc deficient endothelial cells on erythroid cell differentiation. Our studies indicate that c-Myc has a context-dependent role in mediating the function of Apc in hematopoiesis.
2020-08-18 | GSE156361 | GEO
Project description:Tumours depend on altered rates of protein synthesis for growth and survival, suggesting that mechanisms controlling mRNA translation may be exploitable for therapy. Here, we show that loss of APC, which occurs almost universally in colorectal tumours, strongly enhances the dependence on the translation initiation factor eIF2B5. Depletion of eIF2B5 induces an integrated stress response and enhances translation of MYC via an internal ribosomal entry site. This perturbs cellular amino acid and nucleotide pools and strains energy resources and causes MYC-dependent apoptosis. eIF2B5 limits MYC expression and prevents apoptosis in APC-deficient murine and patient-derived organoids and in APC-deficient murine intestinal epithelia in vivo. Conversely, the high MYC levels present in APC-deficient cells induce phosphorylation of eIF2alpha via the GCN2 and PKR kinases. Pharmacological inhibition of GCN2 phenocopies eIF2B5 depletion and has therapeutic efficacy in tumour organoids, demonstrating that a negative MYC/eIF2alpha feedback loop constitutes a targetable vulnerability of colorectal tumours.
2019-11-04 | GSE106858 | GEO
Project description:One of the transcriptional targets of b-catenin/TCF and a key downstream effector of the WNT/b-catenin pathway in several tissues is the MYC proto-oncogene, which encodes for a transcription factor that is a master regulator of proliferation- and growth-related genes. However, several evidences indicate that this epistatic relationship does not seem to occur in liver: indeed Myc was not induced upon b-catenin activation driven by APC loss, and Myc deletion in hepatocytes does not suppress the effects of APC loss on cell proliferation and liver zonation. Besides, there are indications that the two pathways can be independently activated, and cooperate during tumorigenesis. In particular, MYC amplification and b-catenin mutations showed a tendency toward co-occurrence in either adult HCC or aggressive childhood hepatoblastoma, and MYC-driven HCC in experimental mouse models frequently acquired activating mutations in b-catenin. In order to address whether these observations reflect a functional cross-talk between the two pathways that may occur in a specific molecular subgroup of HCC patients, we generated a new mouse model allowing conditional activation of MYC and -catenin in hepatocytes. This model demonstrated a strong cooperativity between the two oncogenes in promoting liver tumorigenesis. Our data indicate that this cooperation occurs mainly through unrestrained proliferation of liver cells that requires the activity of the transcriptional co-factors Yap and Taz.
2020-05-12 | GSE138296 | GEO