Expression data derived from adenocarcinoma or neuroendocrine prostate cancer of TRAMP and SPARC deficient TRAMP mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE242811 | GEO | 2024/07/01
REPOSITORIES: GEO
Similar Datasets
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:Introduction: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer, exhibiting rapid progression and is unresponsive to hormone therapy. Reliable prognostic assays and more effective treatments are critically required. However, the research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we successfully developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation from prostate adenocarcinoma. By comparing gene expression profiles of the parental adenocarcinoma line (LTL331) and the NEPC subline (LTL331R), we identified DEK, a gene not previously reported in prostate cancer, as a potential biomarker and target for NEPC. Methods: DEK protein expression in patient tissue-derived xenograft models and clinical samples was assessed by immunohistochemistry. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis. Results: Elevated DEK protein expression was observed in all clinical NEPC cases, which is distinct from their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration resistant prostate cancer (29.55%). Increased DEK expression is an independent clinical risk factor and is associated with shorter disease free survival in hormonal naïve prostate cancer patients. Reduction of DEK expression in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. Conclusions: The results suggest that DEK may play an important role in the progression of prostate cancer, especially NEPC and provide a potential biomarker to aid risk stratification of prostate cancer and a novel therapeutic target for treating NEPC. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis.
2015-01-15 | E-GEOD-61214 | biostudies-arrayexpress
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
Project description:Fatal neuroendocrine (NE) prostate cancer evolves from castration-resistant adenocarcinoma as a mechanism of resistance to androgen deprivation/anti androgen receptor therapies. Evidence suggests the microenvironment as a possible source of soluble factors mediating neuroendocrine differentiation (NED), but molecular mechanisms are unknown. Using a transgenic mouse model we show that upon castration tumor cells up-regulate GRP78, which triggers a cascade leading to down-regulation of the matricellular protein SPARC in the nearby stroma. SPARC loss allows stroma cells to release IL-6, a known inducer of NED. A drug targeting GRP78 blocks NED in castrated mice. These events find correlation in prostate cancer patients developing focal NED after androgen deprivation therapies. Our results candidate SPARC and GRP78 for diagnostic and therapeutic purpose, respectively.
2021-07-30 | GSE156033 | GEO
Project description:Gene expression profile of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) reveals murine targets for preclinical development of human prostate cancer therapy In this study, we have generated an open source TRAMP microarray dataset to identify differentially expressed genes from human prostate cancer that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. Affymetrix Mouse 430 2.0 chips were used for microarrays of total RNA from 9 TRAMP tumors and 9 normal prostates (ventral and dorsolateral lobes). Keywords: prostate cancer, TRAMP
2008-12-31 | GSE10525 | 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 TGF pathway, and a role for TGF 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.
2016-01-20 | GSE69903 | GEO
Project description:We reported efficacy of Angelica gigas Nakai (AGN) root ethanol extract and equimolar decursin (D)/decursinol angelate (DA) through daily gavage starting at 8 weeks of age (WOA) to male transgenic adenocarcinoma of mouse prostate (TRAMP) mice such that these modalities suppressed precancerous epithelial lesions in their dorsolateral prostate (DLP) to similar extent, but AGN extract was better than the D/DA mixture at promoting the survival of mice bearing prostate neuroendocrine carcinomas (NECa) to 28 WOA (Tang et al, Cancer Prev Res 2015). Here, we compared by microarray hybridization the mRNA levels in pooled DLP tissues and individual NECa to characterize potential molecular targets of AGN extract and D/DA. Clustering and principal component analyses supported distinct gene expression profiles of TRAMP DLP vs. NECa. Pathway Enrichment, Gene Ontology and Ingenuity Pathway Analyses of differential genes indicated that AGN and D/DA affected chiefly processes of lipid and mitochondrial energy metabolism and oxidation-reduction in TRAMP DLP, while AGN affected neuronal signaling, immune systems and cell cycling in NECa. Protein-Protein Interaction Network analysis predicted and reverse transcription-PCR verified multiple hub genes common in the DLP of AGN- and D/DA-treated TRAMP mice at 28 WOA and select hub genes attributable to the non-D/DA AGN components. The vast majority of hub genes in the AGN-treated NECa differed from those in TRAMP DLP. In summary, the transcriptomic approach illuminated vastly different signaling pathways and networks, cellular processes and hub genes of two TRAMP prostate malignancy lineages and their associations with the interception efficacy of AGN and D/DA.
2021-01-15 | GSE164854 | GEO
Project description:Gene expression profile of Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) reveals murine targets for preclinical development of human prostate cancer therapy; In this study, we have generated an open source TRAMP microarray dataset to identify differentially expressed genes from human prostate cancer that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. Affymetrix Mouse 430 2.0 chips were used for microarrays of total RNA from 9 TRAMP tumors and 9 normal prostates (ventral and dorsolateral lobes). Experiment Overall Design: normal prostate vs. TRAMP
2009-01-14 | E-GEOD-10525 | biostudies-arrayexpress
Project description:Neuroendocrine prostate cancer (NEPC) is proliferative, invasive, and untreatable. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. In this study we modeled the development of NEPC from conventional prostatic adenocarcinoma using a unique patient-derived xenograft and identified up-regulation of the placental gene PEG10. We found that the androgen receptor and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at different stages of NEPC development. In vitro, PEG10 promoted cell cycle progression from G0/G1 in the context of TP53 loss, and regulated Snail expression via TGF-β signaling to promote invasion. Finally we show in vivo proof of principal using antisense oligonucleotide that PEG10 is a novel therapeutic target for NEPC. Six patient-derived xenograft tumors from the LTL331 xenograft lineage (PMID: 24356420; http://www.livingtumorcentre.com/) after differing lengths of time post-host castration. No replicates.
2015-01-05 | E-GEOD-59985 | biostudies-arrayexpress