RNA-seq of human prostate cancer cell lines grown as orthotopic tumour models of castration resistant prostate cancer
Ontology highlight
ABSTRACT:
INSTRUMENT(S): NextSeq 500
ORGANISM(S): Homo sapiens
SUBMITTER: Mark Salji
PROVIDER: E-MTAB-9831 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Purpose: Resistance to androgen deprivation therapies is a major driver of mortality in advanced prostate cancer. Therefore, there is a need to develop new pre-clinical models that allow the investigation of resistance mechanisms and the assessment of drugs for the treatment of castration resistant prostate cancer. Methods: We generated two novel cell line models (LAPC4-CR and VCaP-CR) which were derived by passaging LAPC4 and VCaP cells in vivo and in vitro under castrate conditions. We performed detailed transcriptomic (RNA-seq) to delineate expression differences between castration-sensitive and castration-resistant cell lines. LAPC4-CR and VCaP-CR cell lines maintained AR expression, but exhibited distinct expression changes on the mRNA and protein level. Integrated analyses including data from LNCaP and the previously described castration resistant LNCaP-abl cells revealed an expression signature of castration resistance. Results: Integrated analyses including data from LNCaP and the previously described castration resistant LNCaP-abl cells revealed an expression signature of castration resistance.
2021-06-27 | GSE178963 | GEO
Project description:Expression of HS3ST1 is markedly upregulated in castration-resistant prostate cancer, which proliferates hormone-independently. In a novel mechanism, EGFR–ERK1/2 signaling is activated via 3-O-sulfated HS and EGF/HB-EGF binding in castration-resistant prostate cancer.
2023-07-20 | GSE223471 | GEO
Project description:Castration-resistant prostate cancer is a lethal disease. The cell type(s) that survive androgen-deprivation remain poorly described despite global efforts to understand the various mechanisms of therapy resistance. We recently identified in wild type mouse prostates a rare population of luminal progenitor cells that we called LSCmed according to their FACS profile (Lin?/Sca-1+/CD49fmed). Here we investigated the prevalence and castration resistance of LSCmed in various mouse models of prostate tumorigenesis. In intact mice, we show that LSCmed prevalence remains low (5-10% of epithelial cells) when prostatic androgen receptor signaling unaltered (malignant Hi-Myc mice) but significantly increases in models exhibiting reduced prostatic androgen receptor signaling, rising up to 30% in premalignant tumors (Pb-PRL mice) and to >80% in castration-resistant prostate tumors driven by Pten loss (Ptenpc-/- mice). LSCmed tolerance to androgen deprivation was demonstrated by their persistence (Ptenpc-/-) or further enrichment (Pb-PRL) 2-3 weeks after castration as evidenced by FACS analysis. Transcriptomic analysis revealed that LSCmed represent a unique cell entity as their gene-expression profile is different from luminal and basal/stem cells, but shares markers of each. Their intrinsic androgen signaling is markedly decreased, which explains why LSCmed tolerate androgen-deprivation. This also enlightens why Ptenpc-/- tumors are castration-resistant since LSCmed represent the most prevalent cell type in this model. We validated CK4 as a specific marker for LSCmed on sorted cells and prostate tissues by immunostaining, allowing for the detection of LSCmed in various mouse prostate specimens. In castrated Ptenpc-/- prostates, BrdU staining revealed massive proliferation of CK4+ cells, further demonstrating their key role in castration-resistant prostate cancer progression. In all, this study identifies LSCmed as a probable source of prostate cancer relapse after androgen deprivation and as a new therapeutic target for the prevention of castrate-resistant prostate cancer.
2017-08-15 | E-MTAB-4991 | biostudies-arrayexpress
Project description:Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance in early prostate cancer, other factors such as c-Myc and the E2F family also play a role in later stage disease. Hes6 is a transcription co-factor that has been associated with neurogenesis during gastrulation, a neuroendocrine phenotype in the prostate and metastasis in breast cancer but its role in prostate cancer remains uncertain. Here we show that Hes6 is controlled by c-Myc and AR and drives castration resistance in prostate cancer. Hes6 activates a cell-cycle enhancing transcriptional network that maintains tumour growth and nuclear AR localization in castrate conditions. We show aphysical interaction between E2F1 and both Hes6 and AR, and suggest a co-dependency of these transcription factors in castration-resistance. In the clinical setting, we have uncovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted. We have therefore shown for the first time the critical role of Hes6 in the development of CRPC and identified its potential in patient specific therapeutic strategies. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-04-17 | E-GEOD-36526 | biostudies-arrayexpress
Project description:Bulk RNA sequencing of peripheral blood neutrophils from prostate cancer at different stages of disease progression, including localized disease, hormone-sensitive- and castration-resistant metastatic prostate cancer
2023-12-13 | GSE197609 | GEO
Project description:Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. Here we show that Hes6 is up-regulated in aggressive human prostate cancer and drives castration-resistant tumour growth in the absence of ligand binding by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for other transcription factors including E2F1. In the clinical setting, we have uncovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted with restoration of sensitivity to castration. AR and E2F1 ChIPseq from multiple simultaneous LNCaP cell replicates with and without bicalutamide
2014-04-17 | E-GEOD-49832 | biostudies-arrayexpress
Project description:We compared 22 primary Pca (hormone-dependent) versus 29 metastatic Pca (CRPC). The expression of genes related to cell cycle, proliferation, DNA synthesis, and androgen metablism are significantly increased in CRPC group. The expression of AR-stimulated genes were partially reactivated. TMPRSS2-ERG fusion status was determined for the samples by PCR. The expression of ERG was highly increased in fusion positive versus negative. 120 snap-frozen CT-guided bone marrow biopsies from patients with castration-resistant prostate cancer were collected as a source of material. 29 independent biopsies containing mostly tumor were identified as CRPC group through carefully microscopical examination. 4 samples containing no tumor were identified as normal bone marrow group. Primary tumor was isolated by LCM from frozen biopsies of hormone-naive patients. 22 samples were selected as primary PCa group.
2011-09-21 | E-GEOD-32269 | biostudies-arrayexpress
Project description:Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. Here we show that Hes6 is up-regulated in aggressive human prostate cancer and drives castration-resistant tumour growth in the absence of ligand binding by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for other transcription factors including E2F1. In the clinical setting, we have uncovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted with restoration of sensitivity to castration.
2014-04-17 | GSE49832 | GEO
Project description:Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance in early prostate cancer, other factors such as c-Myc and the E2F family also play a role in later stage disease. Hes6 is a transcription co-factor that has been associated with neurogenesis during gastrulation, a neuroendocrine phenotype in the prostate and metastasis in breast cancer but its role in prostate cancer remains uncertain. Here we show that Hes6 is controlled by c-Myc and AR and drives castration resistance in prostate cancer. Hes6 activates a cell-cycle enhancing transcriptional network that maintains tumour growth and nuclear AR localization in castrate conditions. We show aphysical interaction between E2F1 and both Hes6 and AR, and suggest a co-dependency of these transcription factors in castration-resistance. In the clinical setting, we have uncovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted. We have therefore shown for the first time the critical role of Hes6 in the development of CRPC and identified its potential in patient specific therapeutic strategies. This SuperSeries is composed of the SubSeries listed below.
2014-04-17 | GSE36526 | GEO
Project description:The integration of diverse ‘omic’ datasets will increase our understanding of the key signaling pathways that drive disease. Here, we used clinical tissue cohorts corresponding to lethal metastatic castration resistant prostate cancer (CRPC) obtained at rapid autopsy to integrate mutational, transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied Diffusion through Interacting Events (TieDIE), we integrated differentially expressed transcriptional master regulators, functionally mutated genes, and differentially ‘activated’ kinases in CRPC tissues to synthesize a robust signaling network consisting of pathways with known and novel gene interactions. For 6 individual CRPC patients for which we had transcriptomic and phosphoproteomic data we observed distinct pathway activation states for each patient profile. In one patient, the activated pathways were strikingly similar to a prostate cancer cell line, 22Rv1, providing us with a good pre-clinical model to test targeted, combination therapies. In all, synthesis of multiple ‘omic’ datasets revealed a plethora of pathway information suitable for targeted therapies in lethal prostate cancer.
2016-08-19 | PXD002286 | Pride