Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA184722 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Androgen signalling through the androgen receptor (AR) plays a critical role in prostate cancer (PCa) initiation and progression. Estrogen and the estrogen receptor, in synergy with androgen, are essential for cell growth of the normal and malignant prostate. However, the exact role that estrogen plays in prostate carcinogenesis, and the precise mechanisms involved, remain unclear. We have previously demonstrated the metastasis-promoting effect of an estrogen receptor Beta (ERβ) agonist (genistein) and the inhibitory action of an anti-estrogen (ICI 182, 780) in patient-derived PCa xenograft models mimicking localized and metastatic disease. In this study, we compared the gene expression profiles of treated and untreated PCa xenografts using microarrays to identify a unique set of genes that were both up-regulated by genistein treatment and down-regulated by the anti-estrogen, ICI 182,780. Five of the six genes identified from this comparison belonged to the metallothionein (MT) gene family. Knock-down of ERβ led to a reduction in MT gene expression, confirming its role in regulating these genes. Using qRT-PCR, the differences in expression levels were validated in the metastatic and non-metastatic LTL313 PCa xenograft tumour lines, both of which were originally derived from the same PCa patient. Together our data provides evidence for the role of ERβ signalling in PCa metastasis and implicates estrogen-stimulated MT gene expression in this process. Three samples each (total RNA extracted from three tumours of three different animals from each group) for control, genistein and ICI were used for the array.
2012-12-27 | E-GEOD-43146 | biostudies-arrayexpress
Project description:Androgen signalling through the androgen receptor (AR) plays a critical role in prostate cancer (PCa) initiation and progression. Estrogen and the estrogen receptor, in synergy with androgen, are essential for cell growth of the normal and malignant prostate. However, the exact role that estrogen plays in prostate carcinogenesis, and the precise mechanisms involved, remain unclear. We have previously demonstrated the metastasis-promoting effect of an estrogen receptor Beta (ERβ) agonist (genistein) and the inhibitory action of an anti-estrogen (ICI 182, 780) in patient-derived PCa xenograft models mimicking localized and metastatic disease. In this study, we compared the gene expression profiles of treated and untreated PCa xenografts using microarrays to identify a unique set of genes that were both up-regulated by genistein treatment and down-regulated by the anti-estrogen, ICI 182,780. Five of the six genes identified from this comparison belonged to the metallothionein (MT) gene family. Knock-down of ERβ led to a reduction in MT gene expression, confirming its role in regulating these genes. Using qRT-PCR, the differences in expression levels were validated in the metastatic and non-metastatic LTL313 PCa xenograft tumour lines, both of which were originally derived from the same PCa patient. Together our data provides evidence for the role of ERβ signalling in PCa metastasis and implicates estrogen-stimulated MT gene expression in this process.
2012-12-27 | GSE43146 | GEO
Project description:KAP1 promotes proliferation and metastatic progression of breast cancer cells
| PRJNA261739 | ENA
Project description:To identify molecular effects of genistein on mRNA levels in prostate cancer, we compared gene expression profiles of genistein-treated tumors with placebo-treated samples. There were 628 probes that reached nominally significant p-values. The genes that were differentially expressed between genistein and placebo samples were involved in angiogenesis, apoptosis, epithelial to mesenchymal transition, and tumor progression. Gene enrichment analysis suggested that PTEN and PDGF were activated, while MYC, beta-estradiol, glucocorticoid receptor NR3C1, and interferon-gamma were repressed in response to genistein treatment. These findings highlight the effects of genistein on global changes in gene expression in prostate cancer and its effects on molecular pathways involved in prostate tumorigenesis.
2017-06-23 | GSE84748 | GEO
Project description:Through digital rectal examinations and routine prostate-specific antigen (PSA) screening, early treatment of prostate cancer has become possible. However, prostate cancer is a complex and heterogeneous disease. In many patients, cancer cells can invade adjacent tissues and metastasize to other tissues, resulting in difficultly to cure. For the treatment of primary and metastatic prostate cancer, a significant problem is how to improve its survival time. Here, we collect 7 untreated primary and metastatic prostate cancer and 6 benign prostate hyperplasia samples under ultrasound guidance by experienced radiologists using the 18-G needle. Through mass spectrometry, we have completely depicted the protein atlas of primary and metastatic prostate cancer and benign prostate hyperplasia. Through bioinformatics analysis, experimental verification, and combined clinical data, we discover that the ribosome signaling pathway promotes the progression of prostate cancer and is associated with a poor prognosis. Among them, Mrpl1, Mrpl4, and Mrpl16 may be biomolecular markers for diagnosis and prognosis.
2021-09-05 | PXD028211 |
Project description:PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease. To identify additional pathway alterations that cooperate with PTEN loss in prostate cancer progression, we surveyed human prostate cancer tissue microarrays and found that the RAS/MAPK pathway is significantly elevated both in primary and metastatic lesions. In an attempt to model this event, we crossed conditional activatable K-rasG12D/WT mice with the prostate conditional Pten deletion model we previously generated. Although RAS activation alone cannot initiate prostate cancer development, it significantly accelerated progression caused by PTEN loss, accompanied by epithelial-to-mesenchymal transition (EMT) and macrometastasis with 100% penitence. A novel stem/progenitor subpopulation with mesenchymal characteristics was isolated from the compound mutant prostates, which was highly metastatic upon orthotopic transplantation. Importantly, inhibition of RAS/MAPK signaling by PD325901, a MEK inhibitor, significantly reduced the metastatic progression initiated from transplanted stem/progenitor cells. Collectively, these data indicate that activation of RAS/MAPK signaling serves as a potentiating second hit to alteration of the PTEN/PI3K/AKT axis and co-targeting both pathways is highly effective in preventing the development of metastatic prostate cancers. Murine mutants with prostate specific loss of Pten and K-ras activation (K-rasG12D) under regulation of the probasin promoter developed high grade, invasive prostate cancer. RNA was extracted from dissected prostate lobes from individual mutants with pathology thought to closely mimic human disease. Prostate tissue was subject to RNA extraction and hybridization on Affymetrix cDNA microarrays.
2012-02-28 | E-GEOD-34839 | biostudies-arrayexpress
Project description:EphA6 promotes angiogenesis and prostate cancer metastasis and is associated with human prostate cancer progression
| PRJNA276564 | ENA
Project description:The current view of cellular transformation and cancer progression supports the notion that cancer cells must reprogram their metabolism in order to survive and progress in different microenvironments. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator PGC1α suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is consistently down-regulated in multiple prostate cancer patient datasets and its alteration is associated with reduced disease-free survival and metastasis. Genetically engineered mouse model studies revealed that compound prostate epithelium-specific deletion of Pgc1a and Pten promotes prostate cancer progression and metastasis, whereas, conversely, PGC1α expression in cell lines inhibits the pre-existing metastatic capacity. Through the application of integrative metabolomics and transcriptomics we demonstrate that PGC1α expression in prostate cancer is sufficient to elicit a global metabolic rewiring that opposes cell growth, consisting of sustained oxidative metabolism at the expense of anabolism. This metabolic program is regulated downstream the Oestrogen-related receptor alpha (ERRα), and PGC1α mutants lacking ERRα activation capacity lack metabolic rewiring capacity and metastasissuppressive function. Importantly, an ERRα signature in prostate cancer recapitulates the prognostic features of PGC1A. Our findings uncover an unprecedented causal contribution of PGC1α to the metabolic switch in prostate cancer and to the suppression of metastatic dissemination. Total RNA was isolated from prostate cancer cell line PC3 expressing or not PGC1a (for induction, cells were treated with doxycycline for 2 passages)
2016-03-16 | E-GEOD-75193 | biostudies-arrayexpress
Project description:Prior studies support the notion that the experimental chemopreventive agent, genistein, inhibits prostate cancer (PCa) cell movement in humans and that this in turn inhibits metastatic spread, thereby preventing PCa-specific death. As many effects have been ascribed to genistein, it has been considered a non-specific agent. However, its effects are concentration-dependent, and the vast majority of studies use concentrations greater than 3 logs above those associated with dietary consumption. Genistein is found in soy, and individuals consuming soy-based diets have blood concentrations of free genistein in the low nanomalar range. Using dosing guided by phase I pharmacokinetic studies in US men, prospective treatment of men on a phase II trial with genistein for one month prior to radical prostatectomy for localized PCa. Here we conducted an unbiased screening for effects of genistein in prostate as well as evaluate changes between normal and cancer cells.
2019-03-16 | GSE128339 | GEO
Project description:The placental gene PEG10 promotes progression of neuroendocrine prostate cancer [Expression]
| PRJNA257216 | ENA