Ena-DATASET-MUG-17-05-2013-08:29:19:239-74 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001000396 | EGA |
REPOSITORIES: EGA
Publications
Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing.
Heitzer Ellen E Ulz Peter P Belic Jelena J Gutschi Stefan S Quehenberger Franz F Fischereder Katja K Benezeder Theresa T Auer Martina M Pischler Carina C Mannweiler Sebastian S Pichler Martin M Eisner Florian F Haeusler Martin M Riethdorf Sabine S Pantel Klaus K Samonigg Hellmut H Hoefler Gerald G Augustin Herbert H Geigl Jochen B JB Speicher Michael R MR
Genome medicine 20130405 4
<h4>Background</h4>Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively.<h4>Methods</h4>We wanted to ...[more]
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Project description:We report RNA sequencing data on serial biopsies of prostate cancer VCaP xenografts as the tumors pass from androgen-sensitivity (Pre-Cx), to castration resistance (CRPC, castration resistant prostate cancer), onto resistance to dual therapy with abiraterone plus enzalutamide (AER). From comparison of these RNAseq data sets, we were able to determine differentially expressed genes between the AER/CRPC and Pre-Cx states that could mediate resistance to androgen deprivation therapies.
2018-12-26 | GSE109708 | GEO
Project description:Introduction: Androgen deprivation therapy (ADT) remains the primary treatment for advanced prostate cancer (PCa). The efficacy of ADT has not been rigorously evaluated by demonstrating suppression of prostatic androgen activity at the target tissue and molecular level. We determined the efficacy and consistency of medical castration in suppressing prostatic androgen levels and androgen-regulated gene-expression. Design: Androgen levels and androgen-regulated gene-expression (by microarray-profiling, qRT-PCR and immunohistochemistry) were measured in prostate samples from a clinical trial of short-term castration (1 month) using the GnRH-antagonist, Acyline, vs. placebo in healthy men. To assess the effects of long-term ADT, gene-expression measurements were evaluated at baseline and after 3, 6 and 9 months of neoadjuvant ADT in prostatectomy samples from men with localized PCa. Results: Medical castration reduced tissue androgens by 75% and reduced the expression of several androgen-regulated genes (NDRG1, FKBP5, TMPRSS2). However, many androgen-responsive genes, including the androgen receptor (AR) and PSA, were not suppressed after short-term castration, nor after 9 months of neoadjuvant ADT. Significant heterogeneity in PSA and AR protein expression was observed in PCa samples at each time-point of ADT. Conclusions: Medical castration based on serum testosterone levels cannot be equated with androgen ablation in the prostate microenvironment. Standard androgen deprivation does not consistently suppress androgen-dependent gene-expression. Suboptimal suppression of tumoral androgen activity may lead to adaptive cellular changes allowing PCa cell survival in a low androgen environment. Optimal clinical efficacy will require testing of novel approaches targeting complete suppression of systemic and intracrine contributions to the prostatic androgen microenvironment. Keywords: prostate, androgen, Acyline, microarray, immunohistochemistry
2007-10-25 | GSE8466 | GEO
Project description:Androgen deprivation is a standard of care front-line therapy for human prostate cancer, however, majority of patients will eventally develop resistance to androgen deprivation. In this study, using a human prostate cancer xenograft model -LuCaP35, we examiend the gene expression changes after castration. We compare the gene expression of 5 LuCaP35 xenografts from non-treated mice (Control), and 5 androgen-deprived LuCaP35 xenografts from castrated mice (Castration).
2011-12-06 | E-GEOD-33316 | biostudies-arrayexpress
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
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Project description:Androgen deprivation is a standard of care front-line therapy for human prostate cancer, however, majority of patients will eventally develop resistance to androgen deprivation. In this study, using a human prostate cancer xenograft model -LuCaP35, we examiend the gene expression changes after castration.
2011-12-06 | GSE33316 | GEO
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2021-04-06 | GSE171491 | GEO
Project description:Prostate cancer is the most common, lethal malignancy in men. Although androgen withdrawal therapies are used to treat advanced disease, progression to a castration-resistant, end-stage is the usual outcome. In this study, the tested hypothesis was that the androgen receptor remains essential for the growth and viability of castration-resistant disease. Knocking down the androgen receptor in well-established tumors grown in castrated mice caused growth arrest, decreased serum PSA, and frequently regression and total eradication of tumors. Growth control of castration-resistant tumors appeared to be linked to the extent of androgen receptor knockdown, which triggers upregulation of many genes involved in apoptosis, cell cycle arrest, and inhibition of tumorigenesis and protein synthesis. Our findings provide proof of principle that in vivo knockdown of the androgen receptor is a viable therapeutic strategy to control and possibly eradicate prostate cancers that have progressed to the lethal castration-resistant state.
2009-02-20 | GSE13332 | GEO
Project description:Prostate cancer (PCa) is heterogeneous containing both phenotypically differentiated and undifferentiated tumor cells. An important unanswered question is whether these two populations of PCa cells are functionally different. Here we report the distinct molecular, cellular, and tumor-propagating properties of PCa cells that express high (i.e., PSA+) and low (PSA-/lo) levels of the differentiation marker PSA (prostatespecific antigen). PSA-/lo PCa cells are quiescent and resistant to multiple stresses including androgen deprivation, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity in male mice. They preferentially express stem cell-associated genes and can undergo asymmetric cell division generating PSA+ cells. Importantly, PSA-/lo PCa cells can initiate robust tumor development in castrated hosts, survive androgen deprivation, and harbor highly tumorigenic castration-resistant PCa cells that can be further enriched using the ALDH+CD44+α2β1+ phenotype. In contrast, PSA+ PCa cells possess more limited tumor-propagating capacity, mainly undergo symmetric division, and are sensitive to castration. Together, our study suggests that PSA-/lo and PSA+ PCa cells are functionally distinct and PSA-/lo cells may represent one critical source of castration-resistant PCa cells. There are 4 sets of human samples in this study corresponding to 4 different prostate cancer patients labeled as HPCa46T, HPCa47T, HPCa49T and HPCa51T. Each set includes 3 technical triplicates (except HPCa46T) that were performed on dual color arrays and each individual array includes comparisons between PSA- (Cy5) and PSA+ (Cy3) cells of the respective patient prostate tumor.
2012-05-09 | E-GEOD-35733 | biostudies-arrayexpress
Project description:Prostate cancer (PCa) is heterogeneous containing both phenotypically differentiated and undifferentiated tumor cells. An important unanswered question is whether these two populations of PCa cells are functionally different. Here we report the distinct molecular, cellular, and tumor-propagating properties of PCa cells that express high (i.e., PSA+) and low (PSA-/lo) levels of the differentiation marker PSA (prostatespecific antigen). PSA-/lo PCa cells are quiescent and resistant to multiple stresses including androgen deprivation, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity in male mice. They preferentially express stem cell-associated genes and can undergo asymmetric cell division generating PSA+ cells. Importantly, PSA-/lo PCa cells can initiate robust tumor development in castrated hosts, survive androgen deprivation, and harbor highly tumorigenic castration-resistant PCa cells that can be further enriched using the ALDH+CD44+α2β1+ phenotype. In contrast, PSA+ PCa cells possess more limited tumor-propagating capacity, mainly undergo symmetric division, and are sensitive to castration. Together, our study suggests that PSA-/lo and PSA+ PCa cells are functionally distinct and PSA-/lo cells may represent one critical source of castration-resistant PCa cells. There are two sets of samples in this study corresponding to two different prostate cancer cell lines LNCaP and LAPC9. Both LNCaP and LAPC9 sets include 3 technical triplicates each that were performed onvdual color arrays and each individual array includes comparison between PSA- (Cy5) and PSA+ (Cy3) cells of the respective cell line.
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