Regulation of gene expression by GLIPR1 in prostate cancer cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32367 | GEO | 2011/09/26
SECONDARY ACCESSION(S): PRJNA147693
REPOSITORIES: GEO
Similar Datasets
Project description:Human glioma pathogenesis-related protein 1 (GLIPR1) and its mouse counterpart, Glipr1 are downregulated in prostate cancer (PCa) and other malignant cell lines, owing partly to methylation in the gene’s regulatory region. Loss of Glipr1 function predisposed mice to tumorigenesis. Restoration of GLIPR1 expression in prostate cancer cells and other malignant cells led to growth suppression and/or apoptosis. Here we show that restoring GLIPR1 expression in PCa cells leads to downregulated c-myc and cell cycle-related c-myc target genes, leading to the inhibition of cell cycle progression. DNA microarray (Illumina HumanHT-12) Prostate cancer cells were transduced with adenovirus-mediated GLIPR1 or control lacZ, grown in complete medium for 24 hours, synchronized by serum starvation for 24 hours, followed by serum restimulation for 30 min. RNA was prepared and subjected to DNA microarray analysis.
2011-09-25 | E-GEOD-32367 | biostudies-arrayexpress
Project description:Despite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. As a consequence, THEM6 loss in CRPC cells significantly alters ER function, preventing lipid-mediated induction of ATF4 and reducing de novo sterol biosynthesis. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.
2021-12-11 | PXD024407 | Pride
Project description:Despite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. As a consequence, THEM6 loss in CRPC cells significantly alters ER function, preventing lipid-mediated induction of ATF4 and reducing de novo sterol biosynthesis. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.
2021-12-11 | PXD024433 | Pride
Project description:Despite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. As a consequence, THEM6 loss in CRPC cells significantly alters ER function, preventing lipid-mediated induction of ATF4 and reducing de novo sterol biosynthesis. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.
2021-12-11 | PXD024456 | Pride
Project description:Hypoxia inducible factor 1 (HIF1) has been shown to cooperate with the androgen receptor (AR) in activation of oncogenic pathways in prostate cancer (PCa). Here we hypothesized that HIF1 also plays a role in PCa response to androgen deprivation therapy (ADT). Comparison of gene expression profiles of androgen exposed (AE) and androgen deprived (AD) CWR22 PCa xenografts identified 596 upregulated and 748 downregulated genes after ADT. Gene ontology (GO) analysis of the differentially expressed genes showed significant enrichment of the biological processes cell proliferation, cell cycle and metabolism and suggested suppression of these processes after ADT. A set of 80 hypoxia-inducible genes were identified in 22Rv1 and LNCaP cell lines treated with hypoxia and showed considerable overlap (53%) with the downregulated genes. Immunostaining of the hypoxia marker pimonidazole showed no difference between AE- and AD-tumors. Comparison of the differentially expressed genes with lists of 1115 direct AR- and 276 direct HIF1-target genes identified 138 AR- and 40 HIF1-targets that were regulated after ADT, including six shared AR- and HIF1-targets for which downregulation was confirmed with RT-PCR. Most HIF1-targets were downregulated and included in the significant biological processes and the set of hypoxia-inducible genes. The downregulation of HIF1-targets was consistent with decreased HIF1A immunostaining in AD- compared to AE-tumors (p=0.002). A decrease in HIF1A immunostaining after ADT was also demonstrated in a cohort of 35 PCa patients (p<0.001). These data suggest suppressed HIF1-signaling after ADT and a shared role of HIF1 and AR in the regressive phase of PCa after ADT. Prostate cancer xenografts were subjected to adrogen deprivation therapy and analysed with regard to changes in gene expressions. Cell culture experiments were performed to generate prostate cancer specific gene lists associated with hypoxia.
2013-10-02 | E-GEOD-42868 | biostudies-arrayexpress
Project description:To investigate the mechanisms underlying castration-resistant prostate cancer (CRPC) development, we used a prostate cancer (PCa) allograft mouse model. In this model, an androgen-dependent (AD) mouse prostate cancer cell line, Myc-CaP, was used. Myc-CaP cells can grow as primary prostate tumors (PPC) in immune competent FVB mice in an AD manner, when host mice are castrated, Myc-CaP allografts shrink (shrunken prostate tumor, S-PC), and later re-grow and become AR-positive CRPC. To compare the gene expression of different stage of PCa, primary cells from PPC, S-PC, and CRPC were isolated and purified. We used RNA-seq to detail the global programme of gene expression underlying castration-resistant prostate cancer (CRPC) development and identified distinct classes of up-regulated or down-regulated genes during this process.
2022-12-15 | GSE208321 | GEO
Project description:Purpose: Treatment-induced tumor dormancy is a state in cancer progression where residual disease is present but remains asymptomatic. Dormant cancer cells are treatment-resistant and responsible for cancer recurrence and metastasis. Prostate cancer (PCa) treated with androgen-deprivation therapy (ADT) often enters a dormant state. ADT-induced PCa dormancy remains poorly understood due to the challenge in acquiring clinical dormant PCa cells and the lack of representative models. We, therefore, aimed to develop clinically relevant models that can be used for studying ADT-induced PCa dormancy. Experimental design: Dormant PCa models were established by castrating mice bearing PCa patient-derived xenografts (PDXs) of hormonal naïve or sensitive PCa. Dormancy status and tumor relapse were monitored and evaluated. Paired pre- and post-castration (dormant) PDX tissues were subjected to morphological and transcriptome profiling analyses. Results: We established eleven ADT-induced dormant PCa models that closely mimicked the clinical courses of ADT-treated PCa. We identified two ADT-induced dormancy subtypes that differed in morphology, gene expression, and relapse rates. We discovered transcriptomic differences in pre-castration PDXs that predisposed the dormancy response to ADT. We further developed a dormancy subtype-based, predisposed gene signature that was significantly associated with ADT response in hormonal naïve PCa and clinical outcome in castration-resistant PCa treated with ADT or androgen-receptor pathway inhibitors.
2022-01-11 | GSE193500 | GEO
Project description:Prostate cancer (PCa) is one of the most prevalent cancer types in men worldwide. However, the main diagnostic tests available for PCa have limitations and need biopsy for histopathological confirmation of the disease. The prostate-specific antigen (PSA) is the main biomarker used for PCa early detection, but an elevated serum concentration is not cancer-specific. Therefore, there is a need for discovery of new non-invasive biomarkers that can accurately diagnose PCa. Here, we used trichloroacetic acid-induced protein precipitation and liquid chromatography-mass spectrometry to profile endogenous peptides in urine samples from patients with PCa (n = 33), benign prostatic hyperplasia (n = 25), and healthy individuals (n = 28). Receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic performance of urinary peptides. In addition, proteasix tool was used for in silico prediction of protease cleavage sites. We found five urinary peptides derived from uromodulin significantly altered between the study groups, all of which were less abundant in the PCa group. In addition, urinary peptides outperformed PSA in discriminating between malignant and benign prostate conditions (AUC = 0.847), showing high sensitivity (81.82%) and specificity (88%). Overall, our study allowed the identification of urinary peptides with potential for use as non-invasive biomarkers in PCa diagnosis.
2022-10-25 | PXD037031 | Pride
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:We profiled genome-wide gene expression of human prostate benign and malignant tissue to identify potential biomarkers and immunotherapy targets. We stratified malignant specimens according to their TMPRSS2:ERG gene fusion status. Radical prostatectomy tissue samples were obtained from the Hershey Foundation Prostate Cancer Serum and Tumor Bank at our institution. Morphologic diagnosis was done by a pathologist. OCT blocks containing >30% of PCa tissue (with Gleason score of 6 or 7) were selected for RNA purification. A biopsy punch was used to select the PCa tissues from the OCT sample blocks. Benign or PCa tissues were homogenized using a TissueLyser (Qiagen) at 28 Hz for 5 min. Total RNA was isolated using Trizol reagent. RNA was quantified by NanoDrop ND-1000 spectrophotometer, and quality was evaluated with Agilent RNA 6000 NanoChip and the 2100 Bioanalyzer, with 28S/18S ratios and RIN determined by 2100 Expert software.
2014-03-18 | E-GEOD-55945 | biostudies-arrayexpress