Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA221334 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Microarray expression data generated to compare the biological impact of KrasG12D allelic duplication in p53null mouse embryonic fibroblasts (MEFs). The RAS/MAPK-signalling pathway is frequently deregulated in non-small cell lung cancer (NSCLC), often through activating mutations in KRAS. Mouse models demonstrated that activation of a single endogenous mutant Kras allele is sufficient to promote lung tumour formation, but acquisition of other genetic alterations is required for malignant progression. Using a well-established lung cancer mouse model we recently demonstrated that advanced KrasG12D-driven spontaneous tumours frequently exhibit enhanced MAPK signalling and KrasG12D allelic enrichment (KrasG12D/Kraswild-type>1), implying that mutant Kras copy gains are positively selected during lung cancer progression. To compare the oncogenic impact of a single mutant allele versus additional mutant Kras copy gain, we carried out a comprehensive analysis of mutant Kras homozygous and heterozygous MEFs and lung cancer cells and show that these genotypes are phenotypically distinct. Title: Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities Authors: Emma M Kerr, Edoardo Gaude, Frances K Turrell, Christian Frezza and Carla P Martins
2016-02-24 | GSE75871 | GEO
Project description:Background: Non-small cell lung cancer (NSCLC) accounts for 81% of all cases of lung cancer and they are often fatal because 60% of the patients are diagnosed at an advanced stage. Besides the need for earlier diagnosis, there is a great need for additional effective therapies. In this work we investigated the feasibility of a lung cancer progression mouse model, mimicking features of human aggressive NSCLC cancer, as biological reservoir for potential therapeutic targets and biomarkers. Results:RNA-seq profiling was performed on total RNA extracted from lungs of 30 week-old p53R172HM-bM-^HM-^Fg/KrasG12D and wild type mice to detect fusion genes and gene/exon-level differential expression associated to the increase of tumor mass. Fusion events were not detected in p53R172HM-bM-^HM-^Fg/KrasG12D tumors. Differential expression at exon-level detected 33 genes with differential exon usage. The study provides a complete transcription overview of the p53R172HM-bM-^HM-^Fg/KrasG12D mouse NSCLC model Lung mRNA profiles of 30-week old wild type (WT) and p53R172HM-bM-^HM-^Fg/KrasG12D mice were generated by deep sequencing, in duplicate using Illumina HiSeq2000.
2013-09-25 | E-GEOD-51144 | biostudies-arrayexpress
Project description:Microarray expression data generated to compare the biological impact of KrasG12D allelic duplication in p53null mouse embryonic fibroblasts (MEFs). The RAS/MAPK-signalling pathway is frequently deregulated in non-small cell lung cancer (NSCLC), often through activating mutations in KRAS. Mouse models demonstrated that activation of a single endogenous mutant Kras allele is sufficient to promote lung tumour formation, but acquisition of other genetic alterations is required for malignant progression. Using a well-established lung cancer mouse model we recently demonstrated that advanced KrasG12D-driven spontaneous tumours frequently exhibit enhanced MAPK signalling and KrasG12D allelic enrichment (KrasG12D/Kraswild-type>1), implying that mutant Kras copy gains are positively selected during lung cancer progression. To compare the oncogenic impact of a single mutant allele versus additional mutant Kras copy gain, we carried out a comprehensive analysis of mutant Kras homozygous and heterozygous MEFs and lung cancer cells and show that these genotypes are phenotypically distinct. Title: Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities Authors: Emma M Kerr, Edoardo Gaude, Frances K Turrell, Christian Frezza and Carla P Martins For MEF generation, KrasLSL-G12D/+ ;p53Fx/Fx mixed background (C57Bl/6/129/Sv) animals were interbred and embryos collected at day E12.5 to overcome KrasLSL-G12D/G12D embryonic lethality and Cre-mediated recombination performed immediately after MEF generation. Cells were cultured in DMEM supplemented with 10% FBS, 2 mM L-Glutamine for one passage and then infected with adenovirus-Cre (5âÃâ107âplaque-forming units/1 x 106 cells). Recombination of LoxP sites was confirmed by PCR analysis. Three independent embryos per genotype were analysed using GPL6887 Illumina MouseWG-6 v2.0 expression beadchip.
2016-02-24 | E-GEOD-75871 | biostudies-arrayexpress
Project description:Background: Non-small cell lung cancer (NSCLC) accounts for 81% of all cases of lung cancer and they are often fatal because 60% of the patients are diagnosed at an advanced stage. Besides the need for earlier diagnosis, there is a great need for additional effective therapies. In this work we investigated the feasibility of a lung cancer progression mouse model, mimicking features of human aggressive NSCLC cancer, as biological reservoir for potential therapeutic targets and biomarkers. Results:RNA-seq profiling was performed on total RNA extracted from lungs of 30 week-old p53R172H∆g/KrasG12D and wild type mice to detect fusion genes and gene/exon-level differential expression associated to the increase of tumor mass. Fusion events were not detected in p53R172H∆g/KrasG12D tumors. Differential expression at exon-level detected 33 genes with differential exon usage. The study provides a complete transcription overview of the p53R172H∆g/KrasG12D mouse NSCLC model
2013-09-25 | GSE51144 | GEO
Project description:Recent data suggests that repression of the Type II TGF-B Receptor (Tgfr2) repression in human lung adenocarcinoma is important for progression from noninvasive to invasive adenocarcinoma. To test this hypothesis in a animal model of non-invasive lung cancer, we generated an inducible, lung specific Tgfbr2 knockout model in the oncogenic Kras mouse. LSL-KrasG12D positive mice were simultaneously backcrossed to C57/Bl6 mice and to the Tgfbr2 flox/flox mice. To induce tumors, 100 _l of saline containing 3x10e10 particles of an adenovirus containing the Cre recombinase (Ad.Cre) was administered to each LSL-KrasG12D mouse intra-nasally. Mice were sacrificed at 7 weeks after administration of Adeno-Cre. We used laser capture microdissection to acquire tumor cells from KrasTgfbr2-/- and KrasTgfbr2 wt mouse tumors.
2011-09-14 | E-GEOD-27717 | biostudies-arrayexpress
Project description:Recent data suggests that repression of the Type II TGF-B Receptor (Tgfr2) repression in human lung adenocarcinoma is important for progression from noninvasive to invasive adenocarcinoma. To test this hypothesis in a animal model of non-invasive lung cancer, we generated an inducible, lung specific Tgfbr2 knockout model in the oncogenic Kras mouse. LSL-KrasG12D positive mice were simultaneously backcrossed to C57/Bl6 mice and to the Tgfbr2 flox/flox mice. To induce tumors, 100 _l of saline containing 3x10e10 particles of an adenovirus containing the Cre recombinase (Ad.Cre) was administered to each LSL-KrasG12D mouse intra-nasally.
2011-09-15 | GSE27717 | GEO
Project description:Recent data suggests that repression of the Type II TGF-B Receptor (Tgfr2) repression in human lung adenocarcinoma is important for progression from noninvasive to invasive adenocarcinoma. To test this hypothesis in a animal model of non-invasive lung cancer, we generated an inducible, lung specific Tgfbr2 knockout model in the oncogenic Kras mouse. LSL-KrasG12D positive mice were simultaneously backcrossed to C57/Bl6 mice and to the Tgfbr2 flox/flox mice. To induce tumors, 100 ul of saline containing 3x10e10 particles of an adenovirus containing the Cre recombinase (Ad.Cre) was administered to each LSL-KrasG12D mouse intra-nasally.
2011-09-15 | GSE27675 | GEO
Project description:Recent data suggests that repression of the Type II TGF-B Receptor (Tgfr2) repression in human lung adenocarcinoma is important for progression from noninvasive to invasive adenocarcinoma. To test this hypothesis in a animal model of non-invasive lung cancer, we generated an inducible, lung specific Tgfbr2 knockout model in the oncogenic Kras mouse. LSL-KrasG12D positive mice were simultaneously backcrossed to C57/Bl6 mice and to the Tgfbr2 flox/flox mice. To induce tumors, 100 ul of saline containing 3x10e10 particles of an adenovirus containing the Cre recombinase (Ad.Cre) was administered to each LSL-KrasG12D mouse intra-nasally. We evaluated the tumor microenvironment response to Tgfbr2 deficient tumor cells. We compared lung tumor cell and stromal cell transcriptional profiles from five-week KrasTgfbr2 -/- and nine-week KrasTgfbr2 WT mice. We used mice at these time points to allow comparison of the stromal compartment of similarly advanced tumors.
2011-09-14 | E-GEOD-27675 | biostudies-arrayexpress
Project description:Using a mouse model of non-small cell lung cancer driven by activated Kras and loss of p53 (KrasG12D;p53fl/fl), we sought to determine which genes change expression in the bulk tumor after repetitive treatment with cispatin. After tumors were treated multiple times with cisplatin and show no further response, we isolated RNA from tumors treated with cisplatin or a vehicle control (PBS) to determine which genes significantly change in expression in chemoresistant bulk tumors.
2021-11-11 | GSE135720 | GEO