Restricted regulation of gene expression in benign prostate epithelial cell models
Ontology highlight
ABSTRACT:
INSTRUMENT(S): G2505. Agilent’s Scan Control software v. A.7.01 and Feature Extraction.
ORGANISM(S): Homo sapiens
SUBMITTER: Anne Margrete Oyan
PROVIDER: E-MTAB-8487 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Prostate cancer is the leading type of cancer diagnosed and the third leading cause of cancer-related deaths worldwide each year in men. The limitations of the current prostate cancer screening test demands new biomarkers for early diagnosis of prostate cancer metastasis to bone. In this study, we performed a deep proteomic analysis of secreted proteins from the prostate cancer bone metastasis cell line, PC-3, and normal prostate cell line, RWPE-1. Here, we quantified 917 proteins and found 68 highly secreted in PC-3 versus RWPE-1 cells using LC-MS/MS. To characterize the highly secreted proteins in the PC-3 cell line to identify biomarker proteins, the quantifiable proteins were divided into four quantitative categories (Q1-Q4). The KEGG pathways of lysine degradation and osteoclast differentiation were enriched in Q4, the highly secreted group. Transforming growth factor (TGF) beta family proteins related to osteoclast differentiation were identified as key regulators in PC-3 cells. Among the 68 highly secreted proteins, pentraxin, follistatin, and TGF-beta family members were confirmed by immunoblots. In particular, serpin B3, modulated by TGF-beta, was detected and its selective expression and secretion in PC-3 cells was confirmed. In the present study, we suggest that serpin B3 is a novel biomarker candidate for diagnosis of prostate cancer metastasis to the bone.
2017-08-30 | PXD006252 | Pride
Project description:GATA2 and FOXA1 are pioneering factors for Androgen Receptor (AR) in prostate cancer cells. Less is known about their role in benign epithelial prostate cells. We investigated if they had the ability to induce differentiation in an undifferentiated prostatic context. Benign basal-like prostate epithelial cells 957E/hTERT-AR cells (a gift from John T. Isaacs lab, Johns Hopkins, MD, USA) were transduced with LentiORF RFP control lentiviral particles. The 957E/hTERT-AR-RFP cells were then transduced with GATA2 and FOXA1 lentiviral particles, and we called the new cell lines hTERT/AR-GATA2 and hTERT/AR-FOXA1, respectively. hTERT/AR-GATA2 is a stable selected cell line and treated with 1 nM anabolic steroids, R1881, or ethanol (ET-OH) for 48 hrs. 957E/hTERT/AR-FOXA1 is a transient cell line, because FOXA1 protein is quickly lost. Twenty four hours post transduction with FOXA1 lentivral particles, 1 nM androgen R1881 or ethanol (ET-OH) were added at time for medium exchange and further treated for 24 hours. GATA-2 and FOXA1 ability to induce differentiation was assessed.
2018-12-01 | E-MTAB-5121 | biostudies-arrayexpress
Project description:Prostate cancer (PCa) is the most common malignant carcinoma that develops in men in Western countries. Up to 30% of patients continue to suffer from disease progression following radical prostatectomy. Therefore, better prognostic markers and molecular targets for cancer treatment are needed. MicroRNA (miRNA) has the potential to be used as biomarkers and as a therapeutic target for the treatment of various cancers, including PCa. Here, to determine how miRNA is involved in PCa progression, we investigated the miRNA expression profiles of 3 PCa cell lines, namely PC3, DU145, and LNCaP, and 2 normal prostate cell lines, namely RWPE-1 and PrSc, using miRNA microarrays. We investigated miRNA genes that were significantly upregulated in PCa cell lines (PC3, DU145, LNCaP) compared with normal cell lines (RWPE-1, PrSc).
2013-09-01 | E-GEOD-40026 | biostudies-arrayexpress
Project description:Transcriptional profiling of RWPE-1 cells stably expressing human androgen receptor (as described in Altintas et al., Mol Cell Endocrinol 2011) treated with a non-metabolisable androgen, R1881 RWPE-1-AR cells were treated with R1881 during 3h or 24h and compared to control not treated cells. Three independent cell culture experiments for each treatment condition (vehicle or R1881 for 3h and 24h).
2011-05-12 | E-GEOD-29232 | biostudies-arrayexpress
Project description:Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a key causal role in tumorigenesis. According to an alternative view, chromosomal instabilities are mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that deregulation of some key pathways, such as MAPK, p53, cell cycle regulation and Polycomb group factors, in addition to activation of several genes like Myc, AML, B-Catenin and the ETS family transcription factors, are key steps in cancer development driven by 20q amplification. Finally we identified 13 cancer initiating genes, located on 20q13, which were significantly overexpressed in many tumors, with expression levels correlated with tumor grade and outcome; these probably play key roles in inducing malignancy via20q amplification. 33 samples were analysised, 12 were in replicate
2010-12-01 | E-GEOD-23038 | biostudies-arrayexpress
Project description:To date there are very few tools to reverse the induced dedifferentiation program in CRPC and to improve the response to the androgen deprivation therapy. Here we report that MAT2A is an important oncogenic cofactor of ERG/EZH2 transcriptional reprogramming impacting significantly the androgenic pathway. Using RNA sequencing coupled with ATAC, here we reveal an important link between ERG/MAT2A and EZH2 that impact on AR signaling pathway. This aberrant epigenetic program can be reversed by MAT2A inhibition which establish a near physiologic AR transcriptional program. Targeting MAT2A alone or in combination with EZH2 inhibitors reverse stemness in multiple models including prostatospheres from human PDX and GEM models of aggressive prostate cancer. Targeting MAT2A enhance the sensitivity to the androgenic blockade by Enzalutamide and to EZH2 inhibitors
2023-07-15 | E-MTAB-12029 | biostudies-arrayexpress
Project description:Induced pluripotent stem (iPS) cells are a valuable resource for discovery of epigenetic changes critical to cell type-specific differentiation. Although iPS cells have been generated from other terminally differentiated cells, the reprogramming of normal adult human basal prostatic epithelial (E-PZ) cells to a pluripotent state has not been reported. Here, we attempted to reprogram E-PZ cells by forced expression of Oct4, Sox2, c-Myc, and Klf4 using lentiviral vectors and obtained embryonic stem cell (ESC)-like colonies at a frequency of 0.01%. These E-PZ-iPS-like cells with normal karyotype gained expression of pluripotent genes typical of iPS cells (Tra-1-81, SSEA-3, Nanog, Sox2, and Oct4) and lost gene expression characteristic of basal prostatic epithelial cells (CK5, CK14, and p63). E-PZ-iPS-like cells demonstrated pluripotency by differentiating into ectodermal, mesodermal, and endodermal cells in vitro, although lack of teratoma formation in vivo and incomplete demethylation of pluripotency genes suggested only partial reprogramming. Importantly, E-PZ-iPS-like cells re-expressed basal epithelial cell markers (CD44, p63, MAO-A) in response to prostate-specific medium in spheroid culture. Androgen induced expression of androgen receptor (AR), and co-culture with rat urogenital sinus further induced expression of prostate-specific antigen, a hallmark of secretory cells, suggesting that E-PZ-iPS-like cells have the capacity to differentiate into prostatic basal and secretory epithelial cells. Finally, when injected into mice, E-PZ-iPS-like cells expressed basal epithelial cell markers including CD44 and p63. When co-injected with rat urogenital mesenchyme, E-PZ-iPS-like cells expressed AR and expression of p63 and CD44 was repressed. DNA methylation profiling identified key pathways and regulators of prostatic differentiation including Wnt5a, BPM7, PTEN, and NKx3.1 using E-PZ-iPS-lke cells. Our results suggest that iPS-like cells can be derived from prostatic epithelial cells. These cells are pluripotent and capable of prostatic differentiation, and therefore provide a novel model for investigating epigenetic changes involved in prostate cell lineage specification. Bisulphite converted DNA from the 10 samples were hybridised to the Illumina Infinium HumanMethylation450K Beadchip v1.2
2016-07-03 | E-GEOD-45469 | biostudies-arrayexpress
Project description:Full title: Comprehensive Characterization of Three-Dimensional Models for Prostate Cancer Growth and Invasion in Laminin-rich Extracellular Matrix Prostate Cancer (PrCa) cells undergo acinar morphogenesis and spheroid formation in three-dimensional (3D) culture, supported by laminin-rich extracellular matrix (lrECM, Matrigel). We developed miniaturized 3D model systems that facilitate investigation of morphogenesis and invasion of normal and PrCa cell lines in lrECM. Primary and non-transformed cell lines formed round structures with strong cell-cell contacts and epithelial polarization, lumen and a complete basal lamina (BL). In contrast, most PrCa cell lines formed either defective, “mass” spheroids with incomplete BL, or invasive “stellate” structures. The bioinformatic analyses of genome-wide mRNA expression data revealed massive alteration of key functional and signaling pathways in 3D cultures, with lipid and steroid metabolism, epigenetic reprogramming, and differentiation-related transcription factors induced across all cell lines by lrECM. In invasive cells, AKT, PI3Kinase, mTOR, and hedgehog signaling pathways were most highly activated, validated by small molecule inhibitors compounds specifically targeting key regulatory molecules. Compounds against AKT and PI3kinase pathways were significantly more effective in invasive cells, compared to mass or round/normal phenotype spheroids, and monolayer culture. A severe morphologic conversion was observed in PC-3 and PC-3M cells, transforming initially round, normal-appearing epithelial spheroids into rapidly invading cell masses. Markers for EMT (epithelial-mesenchymal transition) were highly expressed already in early stage, round spheroids prior to invasive conversion, and were not further increased in invasive cells. This indicates that PrCa cells can display extraordinary plasticity. EMT may be involved in providing a metastable genotype that allows morphological transformation, but is not be required for invasive processes themselves. Total RNA was obtained from non-transformed prostate epithelial cells and prostate cancer cells cultured in monolayer and three-dimensional laminin-rich extracellular matrix (growth factor-reduced Matrigel).
2010-12-06 | E-GEOD-19426 | biostudies-arrayexpress
Project description:To identify which lncRNAs are differentially expressed in prostate cancer, the total RNA from prostate cancer cell lines (PC3, LNCaP), normal epithelial prostatic cells and the pool of 10 prostate tumor tissues and 10 adjacent normal prostate tissues were screened using SurePrint G3 human lncRNA microarrays (Agilent). The SurePrint G3 Human Gene array contains 16,472 lincRNAs and 34,127 mRNA genes. Gene expression in prostate cell lines and pooled tissue samples was measured. Three independent experiments (biological replicates) for cell lines (epithelial cells, PC3 and LNCap) and two independent experiments (technical replicates) for pooled prostate tissues (tumor and adjacent normal) samples were performed.
2014-10-17 | E-GEOD-55909 | biostudies-arrayexpress
Project description:Epidemiological studies provide strong evidence that consumption of cruciferous vegetables, such as broccoli, can significantly reduce the risk of developing cancers. Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing to test the hypothesis that SFN modifies the expression of genes that are critical in prostate cancer progression. Normal prostate epithelial cells, and androgen-dependent and androgen-independent prostate cancer cells were treated with 15 µM SFN and the transcriptome was determined at 6 and 24 hour time points. SFN altered the expression of ~3,000 genes in each cell line and the response was highly dynamic over time. SFN influenced the expression of genes in functional groups and pathways that are critical in cancer including cell cycle, apoptosis and angiogenesis, but the specific effects of SFN differed depending on the state of cancer progression. Network analysis suggested that a transcription factor that is overexpressed in many cancers, Specificity protein 1 (Sp1), is a major mediator of SFN-induced changes in gene expression. Nuclear Sp1 protein was significantly decreased by 24 hour SFN treatment in prostate cancer cells, while a related transcription factor, Sp3 protein was only modestly decreased in androgen-independent prostate cancer cells. Overall, the data show that SFN significantly affects gene expression in normal and cancer cells, with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent. Examination of how the transcriptome of normal and prostate cancer cells is altered by treatment with sulforaphane
2014-07-11 | E-GEOD-48812 | biostudies-arrayexpress