Next-generation RNA sequencing of murine bladder cancer cells isolated from P53/PTEN KO tumors at different stages of the disease.
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PROVIDER: PRJNA575518 | ENA |
REPOSITORIES: ENA
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Project description:Cancer cells from P53/PTEN KO bladder tumors collected at 5, 9, and 13 weeks after adenoviral vector injection.
2021-01-01 | GSE138327 | GEO
Project description:To model the effect of Pten loss on breast cancer, we deleted Pten using a floxed allele and the deleter lines MMTV-Cre(NLST), which targets stem/bi-potent progenitor cells, and WAP-Cre, which targets CD24-positive, pregnancy-identified stem cells/alveolar progenitors. Mammary tumors were detected in WAP-Cre:Ptenf/f females with a latency of 15.2 months. By 18 months, nearly all mice had succumbed to cancer. MMTV-Cre:Ptenf/f mice developed mammary tumors after a longer latency of 26.4 months and reduced penetrance (70%) compared to WAP-Cre:Ptenf/f mice. Tumors from both models were heterogeneous, consisting primarily of differentiated adenocarcinoma (adenomyoepithelioma; ~70%) and adenosquamous carcinoma (20-25%). In addition, a small fraction of tumors was classified as acinar and poorly differentiated adenocarcinoma (4-7%) and adenosarcoma (3-4%). To test the consequences of combined Pten and p53 gene mutation on breast cancer, we deleted both genes via MMTV-Cre or WAP-Cre. Kaplan-Meier tumor free survival curves revealed that WAP-Cre:Ptenf/f:p53f/f and MMTV-Cre:Ptenf/f:p53f/f females developed tumors with reduced latency of 11.3 and 9.8 months, compared with 15.2, 26.4, and 16.9 months for single-mutant WAP-Cre:Ptenf/f, MMTV-Cre:Ptenf/f or MMTV-Cre:p53f/f mice, respectively. In contrast to the heterogeneity of Pten tumors and small percentage of adenosarcomas in these mice, ~70% of Pten:p53 lesions were histologically classified as adeno-sacrcomatoid-like or mesenchymal-like breast cancer, with the rest exhibiting mixed mesenchymal plus adenocarcinomas and differentiated adenocarcinomas. The adeno-sacrcomatoid-like tumors expressed the mesenchymal markers vimentin, K5, SMA, N-cadherin and desmin but not ER, as well as islands of luminal-like K18 expressing cells surrounded by a layer of K14-positive cells. We used microarrays to detect differentially expressed genes in the Pten:p53 double-knock-out vs Pten or p53 single deletions Total RNA was extracted from tumors developed by double Trizol method and hybridized on Affymetrix microarrays.
2012-08-08 | E-GEOD-39955 | biostudies-arrayexpress
Project description:To model the effect of Pten loss on breast cancer, we deleted Pten using a floxed allele and the deleter lines MMTV-Cre(NLST), which targets stem/bi-potent progenitor cells, and WAP-Cre, which targets CD24-positive, pregnancy-identified stem cells/alveolar progenitors. Mammary tumors were detected in WAP-Cre:Ptenf/f females with a latency of 15.2 months. By 18 months, nearly all mice had succumbed to cancer. MMTV-Cre:Ptenf/f mice developed mammary tumors after a longer latency of 26.4 months and reduced penetrance (70%) compared to WAP-Cre:Ptenf/f mice. Tumors from both models were heterogeneous, consisting primarily of differentiated adenocarcinoma (adenomyoepithelioma; ~70%) and adenosquamous carcinoma (20-25%). In addition, a small fraction of tumors was classified as acinar and poorly differentiated adenocarcinoma (4-7%) and adenosarcoma (3-4%). To test the consequences of combined Pten and p53 gene mutation on breast cancer, we deleted both genes via MMTV-Cre or WAP-Cre. Kaplan-Meier tumor free survival curves revealed that WAP-Cre:Ptenf/f:p53f/f and MMTV-Cre:Ptenf/f:p53f/f females developed tumors with reduced latency of 11.3 and 9.8 months, compared with 15.2, 26.4, and 16.9 months for single-mutant WAP-Cre:Ptenf/f, MMTV-Cre:Ptenf/f or MMTV-Cre:p53f/f mice, respectively. In contrast to the heterogeneity of Pten tumors and small percentage of adenosarcomas in these mice, ~70% of Pten:p53 lesions were histologically classified as adeno-sacrcomatoid-like or mesenchymal-like breast cancer, with the rest exhibiting mixed mesenchymal plus adenocarcinomas and differentiated adenocarcinomas. The adeno-sacrcomatoid-like tumors expressed the mesenchymal markers vimentin, K5, SMA, N-cadherin and desmin but not ER, as well as islands of luminal-like K18 expressing cells surrounded by a layer of K14-positive cells. We used microarrays to detect differentially expressed genes in the Pten:p53 double-knock-out vs Pten or p53 single deletions
2012-08-09 | GSE39955 | GEO
Project description:Glioblastoma (GBM) is a highly lethal brain tumor presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as high-grade disease that typically harbors EGFR, PTEN and Ink4a/Arf mutations, and the secondary GBM subtype evolves from the slow progression of low-grade disease that classically possesses PDGF and p53 events1. Here, we show that concomitant CNS-specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute-onset high-grade malignant glioma phenotype with striking clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted p53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of p53 as well the expected PTEN mutations. Integrated transcriptomic profling, in silico promoter analysis and functional studies of murine neural stem cells (NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives elevated c-Myc levels and its associated signature. Functional studies validated increased c-Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of p53-Pten null NSCs as well as tumor neurospheres (TNSs) derived from this model. c-Myc also serves to maintain robust tumorigenic potential of p53-Pten null TNSs. These murine modeling studies, together with confirmatory transcriptomic/promoter studies in human primary GBM, validate a pathogenetic role of a common tumor suppressor mutation profile in human primary GBM and establish c-Myc as a key target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal and tumorigenic potential. We used microarrays to detail the gene expression difference of the p53-null and p53/Pten-doubly null neural stem cell after differentiation . Experiment Overall Design: transcriptome comparisons of 2 independent p53-null with 3 p53/Pten double-null murine NSCs at 1 day post exposure to the differentiation inducer.
2008-10-26 | E-GEOD-12694 | biostudies-arrayexpress
Project description:Soft tissue sarcomas (STS) are a heterogeneous group of tumors associated with poor clinical outcome. While a subset of STS are characterized by simple karyotypes and recurrent chromosomal translocations, the mechanisms driving cytogenetically complex sarcomas are largely unknown. Clinical evidence led us to partially inactivate Pten and p53 in the smooth muscle lineage of mice, which developed high-grade undifferentiated pleomorphic sarcomas (HGUPS), leiomyosarcomas (LMS) and carcinosarcomas (CS) that widely recapitulate the human disease, including the aberrant karyotype and metastatic behavior. Pten was found haploinsufficient whereas the wild-type allele of p53 invariably gained point mutations. Gene expression profile showed upregulated Notch signaling in Pten∆/+p53∆/+ tumors compared to Pten+/+p53∆/+. Consistently, Pten silencing exacerbated the clonogenic and invasive potential of p53-deficient bone marrow-derived mouse mesenchymal stem cells and tumor cells, while activating the Notch pathway. Moreover, the increased oncogenic behavior of Pten∆/+p53∆/+ and shPten-transduced Pten+/+p53∆/+ tumor cells was counteracted by treatment with a gamma secretase inhibitor (GSI), suggesting that the aggressiveness of those tumors can be attributed, at least in part, to enhanced Notch signaling. This study demonstrates a cooperative role for Pten and p53 suppression in complex karyotype sarcomas while establishing Notch as an important functional player in the crosstalk of these pathways during tumor progression. Our results highlight the importance of molecularly subclassifying high-grade sarcoma patients for targeted treatments. Compare Pten∆/+p53∆/+ to Pten+/+p53∆/+ high-grade undifferentiated pleomorphic sarcomas (HGUPS)
2013-01-01 | GSE42103 | GEO
Project description:Our findings suggested that cytokines were upregulated in p53 null primary prostate cells after deleting Rb and/or Pten. Rb and Pten deletion are important for prostate cancer progression. p53-/- Rbf/f vs p53-/- Rbâf/âf primary prostate cells. Three independent experiments were performed. p53-/- Rbf/f vs p53-/- Rbâf/âf Ptenâf/âf primary prostate cells. Four independent experiments were performed.
2015-12-31 | E-GEOD-68904 | biostudies-arrayexpress
Project description:Soft tissue sarcomas (STS) are a heterogeneous group of tumors associated with poor clinical outcome. While a subset of STS are characterized by simple karyotypes and recurrent chromosomal translocations, the mechanisms driving cytogenetically complex sarcomas are largely unknown. Clinical evidence led us to partially inactivate Pten and p53 in the smooth muscle lineage of mice, which developed high-grade undifferentiated pleomorphic sarcomas (HGUPS), leiomyosarcomas (LMS) and carcinosarcomas (CS) that widely recapitulate the human disease, including the aberrant karyotype and metastatic behavior. Pten was found haploinsufficient whereas the wild-type allele of p53 invariably gained point mutations. Gene expression profile showed upregulated Notch signaling in PtenM-bM-^HM-^F/+p53M-bM-^HM-^F/+ tumors compared to Pten+/+p53M-bM-^HM-^F/+. Consistently, Pten silencing exacerbated the clonogenic and invasive potential of p53-deficient bone marrow-derived mouse mesenchymal stem cells and tumor cells, while activating the Notch pathway. Moreover, the increased oncogenic behavior of PtenM-bM-^HM-^F/+p53M-bM-^HM-^F/+ and shPten-transduced Pten+/+p53M-bM-^HM-^F/+ tumor cells was counteracted by treatment with a gamma secretase inhibitor (GSI), suggesting that the aggressiveness of those tumors can be attributed, at least in part, to enhanced Notch signaling. This study demonstrates a cooperative role for Pten and p53 suppression in complex karyotype sarcomas while establishing Notch as an important functional player in the crosstalk of these pathways during tumor progression. Our results highlight the importance of molecularly subclassifying high-grade sarcoma patients for targeted treatments. Compare PtenM-bM-^HM-^F/+p53M-bM-^HM-^F/+ to Pten+/+p53M-bM-^HM-^F/+ high-grade undifferentiated pleomorphic sarcomas (HGUPS) 4 PtenM-bM-^HM-^F/+p53M-bM-^HM-^F/+ were compared to 5 Pten+/+p53M-bM-^HM-^F/+ Keywords: Differential gene expression.
2013-01-01 | E-GEOD-42103 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) is a highly lethal brain tumor presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as high-grade disease that typically harbors EGFR, PTEN and Ink4a/Arf mutations, and the secondary GBM subtype evolves from the slow progression of low-grade disease that classically possesses PDGF and p53 events1. Here, we show that concomitant CNS-specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute-onset high-grade malignant glioma phenotype with striking clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted p53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of p53 as well the expected PTEN mutations. Integrated transcriptomic profling, in silico promoter analysis and functional studies of murine neural stem cells (NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives elevated c-Myc levels and its associated signature. Functional studies validated increased c-Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of p53-Pten null NSCs as well as tumor neurospheres (TNSs) derived from this model. c-Myc also serves to maintain robust tumorigenic potential of p53-Pten null TNSs. These murine modeling studies, together with confirmatory transcriptomic/promoter studies in human primary GBM, validate a pathogenetic role of a common tumor suppressor mutation profile in human primary GBM and establish c-Myc as a key target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal and tumorigenic potential. We used microarrays to detail the gene expression difference of the p53-null and p53/Pten-doubly null neural stem cell after differentiation . Keywords: cell type comparison
2008-10-01 | GSE12694 | GEO
Project description:Our findings suggested that cytokines were upregulated in p53 null primary prostate cells after deleting Rb and/or Pten. Rb and Pten deletion are important for prostate cancer progression.
2015-12-31 | GSE68904 | GEO
Project description:Gene expression profiling analysis (RNAseq) of mouse bladder epithelium from wildtype mice (Arf+/+; p53+/+; Pten+/+) or bladder tumors from Arf-wild-type (Arf+/+; p53f/f; Ptenf/f) or Arfnull (Arff/f; p53f/f; Ptenf/f) mice that had been treated with vehicle or cisplatin
2016-11-15 | GSE89823 | GEO