Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-48522
PROVIDER: PRJNA210424 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Akt signalling leads to stem cell activation and promotes tumour development in epidermis.
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Project description:E2F1 loss induces spontaneous tumour development in Rb-deficient epidermis
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Project description:The specific ablation of Rb1 gene in epidermis (RbF/F;K14cre) promotes proliferation and altered differentiation but does not produce spontaneous tumour development. These phenotypic changes are associated with increased expression of E2F members and E2F-dependent transcriptional activity. Here, we have focused on the possible dependence on E2F1 gene function. We have generated mice that lack Rb1 in epidermis in an inducible manner (RbF/F;K14creERTM). These mice are indistinguishable from those lacking pRb in this tissue in a constitutive manner (RbF/F;K14cre). In an E2F1-null background (RbF/F;K14creERTM; E2F1-/- mice), the phenotype due to acute Rb1 loss is not ameliorated by E2F1 loss, but rather exacerbated, indicating that pRb functions in epidermis do not rely solely on E2F1. On the other hand, RbF/F;K14creERTM;E2F1-/- mice develope spontaneous epidermal tumours of hair follicle origin with high incidence. These tumours, which retain a functional p19arf/p53 axis, also show aberrant activation of βcatenin/Wnt pathway. Gene expression studies revealed that these tumours display relevant similarities with specific human tumours. These data demonstrate that the Rb/E2F1 axis exerts essential functions not only in maintaining epidermal homeostasis, but also in suppressing tumour development in epidermis, and that the disruption of this pathway may induce tumour progression through specific alteration of developmental programs. Gene expression was compared between normal mouse skin, skin from transgenic RbF/F;K14creERTM; E2F1-/- , E2F1-/-, and RbF/F;K14creERTM; E2F1-/- mouse, and carcinomas arising in the skin of RbF/F;K14creERTM; E2F1-/- mouse. All mice were treated with tamoxifen.
2012-08-20 | E-GEOD-38048 | biostudies-arrayexpress
Project description:Crosstalk between deregulated hepatocyte metabolism and cells within the tumour microenvironment, and consequent effects on liver tumourigenesis, are incompletely understood. We show here that hepatocyte specific loss of the gluconeogenic enzyme fructose 1,6-bisphosphatase 1 (FBP1) disrupts liver metabolic homeostasis and promotes tumour progression. FBP1 is universally silenced in both human and murine liver tumours, and hepatocyte-specific Fbp1 deletion results in steatosis, concomitant with activation and senescence of hepatic stellate cells (HSCs), exhibiting a senescence-associated secretory phenotype (SASP). Depleting senescent HSCs by senolytic treatment with dasatinib/quercetin or ABT-263 inhibits tumour progression. We further demonstrate that FBP1-deficient hepatocytes promote HSC activation by releasing HMGB1; blocking its release with the small molecule inflachromene limits FBP1-dependent HSC activation, subsequent SASP development, and tumour progression. Collectively, these findings provide genetic evidence for FBP1 as a metabolic tumour suppressor in liver cancer and establish a critical link between hepatocyte metabolism and HSC senescence that promotes tumour growth.
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Project description:The specific ablation of Rb1 gene in epidermis (RbF/F;K14cre) promotes proliferation and altered differentiation but does not produce spontaneous tumour development. These phenotypic changes are associated with increased expression of E2F members and E2F-dependent transcriptional activity. Here, we have focused on the possible dependence on E2F1 gene function. We have generated mice that lack Rb1 in epidermis in an inducible manner (RbF/F;K14creERTM). These mice are indistinguishable from those lacking pRb in this tissue in a constitutive manner (RbF/F;K14cre). In an E2F1-null background (RbF/F;K14creERTM; E2F1-/- mice), the phenotype due to acute Rb1 loss is not ameliorated by E2F1 loss, but rather exacerbated, indicating that pRb functions in epidermis do not rely solely on E2F1. On the other hand, RbF/F;K14creERTM;E2F1-/- mice develope spontaneous epidermal tumours of hair follicle origin with high incidence. These tumours, which retain a functional p19arf/p53 axis, also show aberrant activation of βcatenin/Wnt pathway. Gene expression studies revealed that these tumours display relevant similarities with specific human tumours. These data demonstrate that the Rb/E2F1 axis exerts essential functions not only in maintaining epidermal homeostasis, but also in suppressing tumour development in epidermis, and that the disruption of this pathway may induce tumour progression through specific alteration of developmental programs.
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Project description:Loss of IL13RA2 promotes metastatic tumour growth in triple-negative breast cancer via increased AKT signalling
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Project description:We investigated changes to murine pancreatic fibroblast gene expression in response to co-culture with 8 murine pancreatic tumour cell sub-populations. Tumours are complex ecosystems where phenotypically diverse tumour cells are embedded in a heterocellular environment. Using an in vitro model of intra-tumoral heterogeneity, we show that clonal tumour cell populations establish distinct interactions with stromal fibroblasts to expand phenotypic diversity across tumour and stromal cell populations. Heterocellular interactions drive differential engagement of tumour cell reciprocal signalling pathways, resulting in normalisation of cell-autonomous differences in MAPK signalling but diversification of AKT signalling. Consequently, tumour cell clones display differential cell-autonomous and non-cell autonomous dependencies. These results demonstrate that tumour-stroma interactions amplify tumour cell autonomous diversity and that our existing perspective on tumour cell heterogeneity underestimates functional diversity.
2019-09-30 | GSE135434 | GEO
Project description:We investigated changes to gene expression in 8 murine pancreatic tumour sub-clones response to co-culture with fibroblasts. Tumours are complex ecosystems where phenotypically diverse tumour cells are embedded in a heterocellular environment. Using an in vitro model of intra-tumoral heterogeneity, we show that clonal tumour cell populations establish distinct interactions with stromal fibroblasts to expand phenotypic diversity across tumour and stromal cell populations. Heterocellular interactions drive differential engagement of tumour cell reciprocal signalling pathways, resulting in normalisation of cell-autonomous differences in MAPK signalling but diversification of AKT signalling. Consequently, tumour cell clones display differential cell-autonomous and non-cell autonomous dependencies. These results demonstrate that tumour-stroma interactions amplify tumour cell autonomous diversity and that our existing perspective on tumour cell heterogeneity underestimates functional diversity.
2019-09-30 | GSE135433 | GEO