Differential gene expression analysis of genes deregulated in Ptch1+/+/Tis21 knockout vs. Ptch1+/+/Tis21 wild-type mice
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PROVIDER: PRJNA737415 | ENA |
REPOSITORIES: ENA
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Project description:Differential gene expression analysis of genes deregulated in Ptch1+/−/Tis21 knockout vs. Ptch1+/−/Tis21 wild-type mice
| PRJNA737417 | ENA
Project description:We generated a new medulloblastoma model by crossing Patched1 heterozygous mice, which develop medulloblastomas with low frequency, with mice lacking the Tis21 gene. Double knock-out mice show a significant increase in medulloblastoma frequency and hyperplastic EGL lesions formed by preneoplastic GCPs. We found that Tis21 deletion does not affect the proliferation of GCPs but it inhibits their differentiation and their ability to migrate outside the EGL, remaining for a prolonged time in the cerebellum proliferative area. We identified as a drug target and major responsible of this migration defect the down-regulation of the promigratory chemokine Cxcl3 rather than a number of down-regulated tumor inhibitors and up-regulated tumor facilitators, and focusing on pathways potentially involved in the tumorigenesis and on putative new drug targets. Among them, we identified the activation of the PI3K/AKT/mTOR pathway that contributes to medulloblastoma development and to high frequency tumorigenesis when the Tis21 gene is down-regulated. Moreover, we used a novel PI3K inhibitor in nodules derived from primary Ptch1+/−/Tis21KO causing a significant reduction of tumor growth, inhibiting proliferation and increasing apoptosis.
2021-07-29 | GSE178124 | GEO
Project description:We generated a new medulloblastoma model by crossing Patched1 heterozygous mice, which develop medulloblastomas with low frequency, with mice lacking the Tis21 gene. Double knock-out mice show a significant increase in medulloblastoma frequency and hyperplastic EGL lesions formed by preneoplastic GCPs. We found that Tis21 deletion does not affect the proliferation of GCPs but it inhibits their differentiation and their ability to migrate outside the EGL, remaining for a prolonged time in the cerebellum proliferative area. We identified as a drug target and major responsible of this migration defect the down-regulation of the promigratory chemokine Cxcl3 rather than a number of down-regulated tumor inhibitors and up-regulated tumor facilitators, and focusing on pathways potentially involved in the tumorigenesis and on putative new drug targets. Among them, we identified the activation of the PI3K/AKT/mTOR pathway that contributes to medulloblastoma development and to high frequency tumorigenesis when the Tis21 gene is down-regulated. Moreover, we used a novel PI3K inhibitor in nodules derived from primary Ptch1+/−/Tis21KO causing a significant reduction of tumor growth, inhibiting proliferation and increasing apoptosis.
2021-07-29 | GSE178122 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE29192: Implication of Nos2 inactivation on the transcriptome of developing cerebellum and Ptch1+/- medulloblastomas (mRNA) GSE29199: Implication of Nos2 inactivation on genomic changes in Ptch1+/- medulloblastomas (array-CGH) Refer to individual Series
2011-12-01 | E-GEOD-29201 | biostudies-arrayexpress
Project description:Ptch1 is the primary receptor for Hedgehog ligands and functions as a negative regulator of the pathway. Ptch1 is upregulated in response to pathway activation and is a direct target of the Gli family of transcription factors that act as the downstream effectors of the pathwat. The goal of this study was to identify tissue specific Gli2 inputs to Ptch1 during development. Additionally, we assessed the prevalence of the repressive chromatin mark (H3K27me3) during directed differentiated of embryonic stem cells into neural progenitors.
2016-06-08 | GSE71199 | GEO
Project description:Ptch1 is a critical negative feedback regulator of the Hedgehog signaling and is upregulated in response to pathway activation. How tissue specific responses are mediated remains unknown. Here, we performed ChIP-seq analysis for epitope-tagged endogenous Gli3 protein to identify limb-specific binding regions within the 500 kb region surrounding Ptch1.
2014-07-03 | GSE52939 | GEO
Project description:Transcriptional profiling to identify genes differentially regulated by stromal specific Ptch1-deficiency during embryonic kidney development. Ptch1 was specifically deleted from stromal progenitors using Foxd1-driven Cre recombinase
2023-06-01 | GSE205921 | GEO
Project description:Chemotherapy resistance supposes a challenge for cancer treatment. Multidrug efflux pumps are able to extrude chemotherapeutic agents increasing their resistance to the treatment. Ptch1 is overexpressed in many metastatic cancers, where it acts as a multidrug efflux pump. Indeed, Ptch1 strongly contributes to the drug efflux in H295R, a human adrenal carcinoma cell line. This efflux is coupled to the proton motive force, restricting Ptch1 drug efflux to acidify environments like cancers. Even though Ptch1 is overexpressed in H295R cells, only 1% of these cells present Ptch1 at the cell surface (Ptch1 positive or PTC subpopulation ). We showed that these Ptch1 positive cells had an increased chemotherapy resistance, migration and clonogenicity compared to the parental cell lines. The RNA seq analysis performed on H295R Ptch1 positive cells and parental H295R cells show an increase of the expression of genes involved in the Hedgehog signaling such as Ptch1, of genes involved in EMT and drug resistance, and of genes involved in stem cell maintenance suggesting that these cells could be cancer stem cells.
2022-01-19 | GSE189424 | GEO
Project description:Ptch1 is a critical negative feedback regulator of the Hedgehog signaling and is upregulated in response to pathway activation. How tissue specific responses are mediated remains unknown. Here, we performed ChIP-seq analysis for epitope-tagged endogenous Gli3 protein to identify limb-specific binding regions within the 500 kb region surrounding Ptch1. ChIP was carried out using an endogenously FLAG-tagged Gli3 protein.
2014-07-03 | E-GEOD-52939 | biostudies-arrayexpress
Project description:Basal cell carcinomas (BCCs) have relative genomic stability and relatively benign clinical behavior but whether these two are related causally is unknown. To investigate the effects of introducing genomic instability into murine BCCs, we have compared ionizing radiation-induced tumorigenesis in Ptch1+/- mice vs. that in Ptch1+/- mice carrying mutant Blm alleles. We found that BCCs in Ptch1+/- Blmtm3Brd/tm3Brd mice had a trend towards greater genomic instability as measured by array CGH and that these mice developed significantly more microscopic BCCs than did Ptch1+/- Blm+/tm3Brd or Ptch1+/- Blm+/+ mice. The mutant Blm alleles also markedly enhanced the formation of rhabdomyosarcomas (RMS), another cancer to which Ptch1+/- mice and PTCH1+/- (basal cell nevus syndrome) patients are susceptible. Highly recurrent but different copy number changes were associated with the two tumor types and included losses of chromosomes 4 and 10 in all BCCs and gain of chromosome 10 in 80% of RMSs. Loss of chromosome 11 and 13, including the Trp53 and Ptch1 loci respectively, occurred frequently in BCCs, suggesting tissue-specific selection for genes or pathways that collaborate with Ptch deficiency in tumorigenesis. Despite the quantitative differences, there was no dramatic qualitative difference in the BCC or RMS tumors associated with the mutant Blm genotype.
2010-01-14 | GSE19880 | GEO