Bulk RNA-sequencing of mouse prostate tumors initiated by transplantation of engineered organoids.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE246251 | GEO | 2024/08/02
REPOSITORIES: GEO
Similar Datasets
Project description:Single-nuclear RNA-sequencing of murine organoid transplant-derived prostate tumors. Purpose: To identify differences in cell composition in murine prostatic tumors and to generate a reference dataset of all major cell types present in mouse prostate tumors Results: We recovered 4,872 cells with a median of 7055.5 UMIs per cell. Conclusions: snRNASeq reveals heterogeneity within neuroendocrine prostate cancer compartment, dominated by an Ascl1+ expression profile with mixed luminal lineage marker genes. snRNASeq recovers all the major epithelial, immune, and stromal cell types in prostate tumors. Spatial transcriptomic profiling of murine prostate tumors. Purpose: To spatially map the major cell types in the mouse prostatic tumors and identify spatially distinct neuroendocrine tumor compartments. Distinct tumor microenvironments were also used for identification of cell:cell signaling axes distributed between the histological subtypes. Conclusions: Spatial transcriptomic profiling of the mouse prostate reveals all major cell types and allows for cell:cell signaling analyses upon integration with our matching snRNA-Seq data
2024-08-02 | GSE246762 | GEO
Project description:Single-nuclear RNA-sequencing of murine organoid transplant-derived prostate tumors. Purpose: To identify differences in cell composition in murine prostatic tumors and to generate a reference dataset of all major cell types present in mouse prostate tumors Results: We recovered 4,872 cells with a median of 7055.5 UMIs per cell. Conclusions: snRNASeq reveals heterogeneity within neuroendocrine prostate cancer compartment, dominated by an Ascl1+ expression profile with mixed luminal lineage marker genes. snRNASeq recovers all the major epithelial, immune, and stromal cell types in prostate tumors. Spatial transcriptomic profiling of murine prostate tumors. Purpose: To spatially map the major cell types in the mouse prostatic tumors and identify spatially distinct neuroendocrine tumor compartments. Distinct tumor microenvironments were also used for identification of cell:cell signaling axes distributed between the histological subtypes. Conclusions: Spatial transcriptomic profiling of the mouse prostate reveals all major cell types and allows for cell:cell signaling analyses upon integration with our matching snRNA-Seq data
2024-08-02 | GSE246768 | GEO
Project description:Flash-frozen prostate tumors collected from patients via radical prostatectomy were analyzed using single-cell ATAC-seq (sci-ATAC-seq). Unique cis- and trans-regulatory signatures between low- and high-grade localized prostate tumors are uncovered.
2021-11-04 | GSE171559 | GEO
Project description:Increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost androgen receptor (AR) signaling. AVPC tumors may also express neuroendocrine markers, termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests kinase signaling may be an important driver of NEPC. To identify targetable kinases in NEPC, we performed global phosphoproteomics comparing AR-negative to AR-positive prostate cancer cell lines and identified multiple altered signaling pathways, including enrichment of RET kinase activity in the AR-negative cell lines. Clinical NEPC and NEPC patient derived xenografts displayed upregulated RET transcript and RET pathway activity. Pharmacologically inhibiting RET kinase in NEPC models dramatically reduced tumor growth and cell viability in mouse and human NEPC models. Our results suggest that targeting RET in NEPC tumors with high RET expression may be a novel treatment option.
2020-05-29 | PXD012971 | Pride
Project description:Increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost androgen receptor (AR) signaling. AVPC tumors may also express neuroendocrine markers, termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests kinase signaling may be an important driver of NEPC. To identify targetable kinases in NEPC, we performed global phosphoproteomics comparing AR-negative to AR-positive prostate cancer cell lines and identified multiple altered signaling pathways, including enrichment of RET kinase activity in the AR-negative cell lines. Clinical NEPC and NEPC patient derived xenografts displayed upregulated RET transcript and RET pathway activity. Pharmacologically inhibiting RET kinase in NEPC models dramatically reduced tumor growth and cell viability in mouse and human NEPC models. Our results suggest that targeting RET in NEPC tumors with high RET expression may be a novel treatment option.
2020-05-29 | PXD012970 | Pride
Project description:Neuroendocrine neoplasms of the gallbladder and liver occur rarely in dogs and humans. A recent reclassification of human neuroendocrine neoplasms by the World Health Organization has refined categorization of these tumors by morphology, replicative indices, and molecular signatures. In humans, these factors correlate with survival outcomes. Improved characterization of these tumors is needed in dogs to identify diagnostic biomarkers and determine therapeutic strategies. To achieve this objective, the proteome of 3 canine hepatobiliary neoplasms was compared to normal canine adrenal and liver tissue from formalin-fixed paraffin-embedded samples. Thirty-two upregulated and 121 downregulated differentially expressed proteins were identified in the hepatobiliary neuroendocrine neoplasm samples. Among the upregulated proteins is galectin-1, a multivalent carbohydrate binding protein known to play a role in lung and pancreatic neuroendocrine neoplasia development and progression in humans. Drugs targeting the galectin family have shown promise as anticancer therapeutics in cervical cancer, prostate cancer, lung and pancreatic neuroendocrine neoplasia in human medicine. Galectin-1 may represent a novel treatment target in hepatobiliary neuroendocrine neoplasia in both humans and dogs.
2023-03-11 | PXD028822 | Pride
Project description:Aggressive cancers and normal stem cells often share similar molecular and functional traits. It is unclear if aggressive phenotypes of prostate cancer molecularly resemble normal stem cells residing within the human prostate. We performed high-throughput RNA sequencing on uncultured, highly purified epithelial populations from human prostates obtained after radical prostatectomy. We found the basal population to be defined by genes associated with developmental programs, epigenetic remodeling, and invasiveness. We further generated a 91-gene basal signature and applied it to gene expression datasets from patients with organ-confined or castration-resistant, metastatic prostate cancer. Metastatic prostate cancer was more enriched for the basal stem cell signature than organ-confined prostate cancer. Moreover, histological subtypes within prostate cancer metastases varied in their enrichment of the stem cell signature with small cell neuroendocrine carcinoma being the most stem cell-like. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common to all three signatures. These results suggest that the most aggressive variants of prostate cancer share a core transcriptional program with normal prostate basal stem cells. Transcriptional analysis of 10 uncultured prostatic basal and luminal populations from either the benign or malignant prostate tissue of 8 human prostate cancer patients by high-throughput RNA-seq
2016-06-01 | E-GEOD-82071 | biostudies-arrayexpress
Project description:Androgen signaling is essential for prostate tumorigenesis. The tumor suppressor p53 has been implicated in prostate cancer progression. Recent genome analysis of human prostate cancers demonstrated that both AR gene amplification and TP53 deletion are frequently altered in advanced prostate cancer. However, the biological role of these dual genetic alterations in prostate tumorigenesis is largely unknown. In addition, there are no biologically relevant models that can be used to assess these genetic abnormalities in the prostate. Here, we report a novel mouse model, in which elevated transgenic AR expression and Trp53 deletion occur simultaneously in mouse prostatic epithelium to mimic what happens in human prostate cancer cells. These compound mice developed an earlier onset of high-grade prostatic intraepithelial neoplasia and accelerated prostate tumors. Histological analysis showed pathological lesions resembling prostatic sarcomatoid and basaloid carcinomas with massive squamous differentiation in the above compound mice. RNA-sequencing analyses showed a robust enrichment of the signature genes for human prostatic basal cell carcinomas in the above prostate tumors. The Master Regulator Analysis further identified SOX2 as a transcriptional regulator in prostatic basal cell tumors. Elevated expression of SOX2 and its downstream target genes were detected in prostatic tumors of the compound mice. Chromatin immunoprecipitation analyses implicate a co-regulatory role of AR and SOX2 in the expression of prostatic basal cell signature genes. These results demonstrate a novel mechanism underlying elevated AR expression and Trp53 deletion induced prostate cancer cell trans-differentiation, aggressiveness, and progression.
2019-04-03 | GSE129243 | GEO
Project description:Protein homeostasis, or proteostasis is critical for organelle function, including mitochondria, but its role in cancer is controversial. Here, we show that transgenic mice expressing the mitochondrial chaperone, TRAP1 in the prostate develop prostatic hyperplasia and cellular atypia. When examined on a Pten+/- background, a common alteration in prostate cancer patients, TRAP1 transgenic mice showed accelerated incidence of invasive prostatic adenocarcinoma, characterized by increased cell proliferation and reduced apoptosis, in situ. Conversely, homozygous deletion of TRAP1 delays prostatic tumorigenesis in Pten+/- mice, without affecting hyperplasia or prostatic intraepithelial neoplasia (PIN). Global RNA sequencing and reverse phase protein array profiling of Pten+/--TRAP1 transgenic tumors reveals modulation of oncogenic networks of cell proliferation, apoptosis, cell motility, DNA damage and metabolism. Mechanistically, reconstitution of Pten+/- prostatic epithelial cells with TRAP1 results in increased cell proliferation, reduced apoptosis, heightened cell invasion, and no changes in mitochondrial bioenergetics. Therefore, TRAP1 promotes invasive prostate cancer, and provides an “actionable” therapeutic target in patients with advanced disease.
2017-05-11 | GSE81316 | GEO
Project description:Osteopontin (OPN) is a secreted glycoprotein, belonging to the non-structural extracellular matrix (ECM), and its over expression in human prostate cancer cells has been associated with disease progression, androgen independence and metastases. Nevertheless the pathophysiology of OPN in prostate tumorigenesis has never been studied. We crossed TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice with OPN deficient (OPN-/-) mice and followed tumor onset and progression in these double mutants. Ultrasound examination detected the early onset of a spherical homogeneous tumor in about 60% of OPN-/- TRAMP mice that seldom occurs in parental TRAMP mice. Histology and immunohistochemistry characterized these tumors for being Tag positive but negative for AR, highly proliferative and endowed of neuroendocrine (NE) features. Gene expression profiling showed up-regulation of genes involved in tumor progression, cell cycle and neuronal differentiation in OPN-deficient versus -sufficient TRAMP tumors. Down-regulated genes included key genes of TGFï?¢ pathway, and a role for TGFï?¢ in NE differentiation of prostate cancer was also confirmed at the protein level. Furthermore, NE genes and particularly those characterizing early prostatic lesions of OPN-deficient mice were found to correlate with those of human NE tumours. These data underscore a novel role of OPN at early stages of prostate cancer growth, protecting against the development of aggressive NE tumors. Total RNA obtained from prostate tumors from 18 and 30 weeks old TRAMP mice, compared to RNA extracted from prostate tumors and prostate tissue from Osteopontin-deleted TRAMP mice
2016-01-20 | E-GEOD-69903 | biostudies-arrayexpress