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:We are comparing differential gene expression in WT vs. CENPF knockout hearts
2012-02-01 | GSE35470 | GEO
Project description:Nrf2 Knockout vs. Wildtype mice
| PRJNA87883 | ENA
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
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: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. We investigated the effect of Blm deficiency on ionizing radiation-induced basal cell carcinoma and rhabdomyosarcoma tumorigenesis in Ptch1+/- mice. Six BCC and five RMS samples were obtained from separate mice. Liver tissue from each mouse was used as the normal reference.
2010-05-15 | E-GEOD-19880 | biostudies-arrayexpress