Ontology highlight
ABSTRACT:
PROVIDER: PRJNA149459 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE32967: Modeling lethal prostate cancer variant with small cell carcinoma features [expression profile] GSE33053: Modeling lethal prostate cancer variant with small cell carcinoma features [genomic profile] Refer to individual Series
2012-01-01 | E-GEOD-33054 | biostudies-arrayexpress
Project description:Modeling lethal prostate cancer variant with small cell carcinoma features [genomic profile]
| PRJNA156569 | ENA
Project description:Modeling lethal prostate cancer variant with small cell carcinoma features [expression profile]
| PRJNA155517 | ENA
Project description:Prostate cancers with clinical features of small cell prostate carcinomas (SCPC) but diverse morphologies share chemotherapy responsiveness with SCPC. We prospectively collected tumor tissues from clinically defined, morphologically diverse, aggressive variant prostate cancers (AVPCa) to determine if they also share molecular features with SCPC
2015-10-10 | GSE73902 | GEO
Project description:MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC including the small cell prostate carcinoma (SCPC) variant with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can both arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. SNP array data of experimentally generated human NEPC tumors and a cell line.
2016-01-29 | GSE77368 | GEO
Project description:MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC including the small cell prostate carcinoma (SCPC) variant with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can both arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. Expression profiling by high throughput sequencing of experimentally generated human tumors with mixed NEPC and prostate adenocarcinoma. Gene expression analysis of laser capture microdissected NEPC and adenocarcinoma from three independent engineered human tumors of mixed NEPC and prostate adenocarcinoma phenotype.
2016-02-06 | E-GEOD-77624 | biostudies-arrayexpress
Project description:Prostate cancer is the Prostate cancer is the most prevalent cancer in men. However, the majority of prostate cancers diagnosed today are indolent with 14% of patients diagnosed with lethal prostate cancer. It is of great importance to determine the molecular features that are involved in the aggressiveness of prostate cancers. To this end, we found that through SWATH-MS proteomics analyses of 108 well-preserved frozen prostate tissues of various disease states, tmost prevalent cancer in men. However, the majority of prostate cancers diagnosed today are indolent with 14% of patients diagnosed with lethal prostate cancer. It is of great importance to determine the molecular features that are involved in the aggressiveness of prostate cancers. To this end, we deployed SWATH-MS proteomics analyses of 108 well-preserved frozen prostate tissues of various disease states.
2022-02-28 | PXD002306 | Pride
Project description:MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC including the small cell prostate carcinoma (SCPC) variant with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can both arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. Expression profiling by high throughput sequencing of experimentally generated human tumors with mixed NEPC and prostate adenocarcinoma.
2016-02-06 | GSE77624 | GEO
Project description:Chromosomal instability (CIN), an ongoing rate of chromosome missegregation during mitosis, is a defining feature of cancer. However, high chromosomal aberrations are detrimental for cell fitness. Here we investigated mechanisms allowing lethal prostate cancer (PCa) to tolerate and survive increasing CIN. Transcriptomic and proteomic analysis of patient datasets and experimental models showed a concomitant increase of CIN and cell division fidelity kinases in lethal PCa. Functional studies identified MASTL as a key kinase to which therapy-resistant PCa cells become addicted to restrain lethal CIN and ensure survival. Combined analysis of transcription factors increased in high CIN PCa patient datasets with detailed promoter analysis identified that MASTL expression is regulated by the Androgen Receptor variant 7 (AR-V7) and E2F7. Finally, targeting MASTL addiction vulnerability in vivo using the small molecule inhibitor GKI-1, improves survival of pre-clinical models. These findings provide proof-of-concept for exploiting CIN levels as a therapeutic approach in cancer.
2023-01-14 | PXD028271 | Pride
Project description:Purpose: Small-cell prostate carcinoma (SCPC) morphology predicts for a distinct clinical behavior, resistance to androgen ablation, and frequent but short responses to chemotherapy. The model systems we report reflect the biology of the human disease and can be used to improve our understanding of SCPC and to develop new therapeutic strategies for it. Experimental Design: We developed a set of CRPC xenografts and examined their fidelity to their human tumors of origin. We compared the expression and genomic profiles of SCPC and large cell neuroendocrine carcinoma (LCNEC) xenografts to those of typical prostate adenocarcinoma xenografts and used a panel of 60 human tumors to validate our findings using immunohistochemistry. Results: We show that SCPC and LCNEC xenograft models retain high fidelity to their human tumors of origin and are characterized by a marked upregulation of UBE2C and other M-phase cell cycle genes in the absence of AR, retinoblastoma (RB1) and cyclin D1 (CCND1) expression and confirm these findings in a panel of CRPC patients’ samples. In addition, array comparative genomic hybridization of the xenografts showed that the SCPC/LCNEC tumors display more copy number variations than the adenocarcinoma counterparts and that there is amplification of the UBE2C locus and microdeletions of RB1 in a subset of these, but no AR nor CCND1 deletions. Moreover, the AR, RB1, and CCND1 promoters showed no CpG methylation in the SCPC xenografts. Conclusion: Modeling human prostate cancer with xenografts allows in-depth and detailed studies of its underlying biology. The detailed clinical annotation of the donor tumors enables associations of anticipated relevance to be made. Futures studies in the xenografts will address the functional significance of the findings. 22 samples were analysed, that included MDA PCa 79 (n = 3), 117-9 (n = 3), 130 (n = 2), 144-4 (n = 4), 144-13 (n = 5), 146-10 (n = 3), 155-2 (n = 1), and 155-12 (n = 1). MDA PCA 79, 117-9 and 130 samples had the pathologic characteristics of prostate adenocarcinoma and were compared against MDA PCA 144-4, 144-13, 146-10 and 155-12 that have the pathologic features of prostate small cell/ large cell neuroendocrine carcinoma
2012-01-01 | E-GEOD-32967 | biostudies-arrayexpress