The role of the mammalian SWI/SNF chromatin remodeling complex in neuroendocrine prostate cancer
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ABSTRACT:
PROVIDER: EGAS00001004177 | EGA |
REPOSITORIES: EGA
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Project description:Here we performed transcriptional profiling of the prostate cancer cell lines LNCaP and 22Rv1 comparing non-targeting siRNA treatment versus siRNAs targeting SWI/SNF complex proteins (SMARCA2, SMARCA4, and SMARCB1). Goal was to determine the effect of SWI/SNF knockdown on gene expression in prostate cancer. Two-condition experiment: non-targeting siRNA versus SWI/SNF-siRNA treated cells. Three SWI/SNF proteins were targeted: SMARCA2, SMARCA4, and SMARB1. Biological replicates: 1 control replicate, 2 treatment replicates per SWI/SNF protein. Technical replicates: 1 replicate per SWI/SNF protein. Cell lines: 22Rv1 and LNCaP.
2013-07-20 | E-GEOD-40384 | biostudies-arrayexpress
Project description:Here we performed transcriptional profiling of the prostate cancer cell lines LNCaP and 22Rv1 comparing non-targeting siRNA treatment versus siRNAs targeting SWI/SNF complex proteins (SMARCA2, SMARCA4, and SMARCB1). Goal was to determine the effect of SWI/SNF knockdown on gene expression in prostate cancer.
2013-07-20 | GSE40384 | GEO
Project description:Knockdown of DHRS7 in the prostate cancer cell line LNCaP was performed for 24h, 36h, and 48h using siRNA.
2022-07-07 | PXD031229 | Pride
Project description:Background: Castration-resistant prostate cancer (CRPC) represents a therapeutic challenge for current medications. Methods: In order to explore the molecular mechanisms involved in CRPC progression and to identify new therapeutic targets, we analyzed a unique sample set of 11 castration-resistant prostate cancers and 7 advanced tumors by array-CGH and gene expression microarrays. The genome-wide DNA and RNA data were integrated to identify genes whose overexpression was driven by their amplification. To assess the functional role of these genes, their expression was analyzed in a transcriptional dataset of 329 clinical prostate cancers and the corresponding gene products were silenced using RNA interference in prostate cancer cells. Results: Six recurrent genetic targets were identified in the CRPCs; ATP1B1, AR, FAM110B, LAS1L, MYC and YIPF6. In addition to AR and MYC, FAM110B emerged as a potential key gene involved in CRPC progression in a subset of the tumors. FAM110B was able to regulate AR signaling in prostate cancer cells and FAM110B itself was regulated by androgens. FAM110B siRNA inhibited the growth of prostate cancer cells in vitro, and this effect was substantially enhanced in androgen deficient conditions. Ectopic FAM110B expression in non-cancerous epithelial prostate cells induced aneuploidy and impaired antigen presentation. Conclusions: The DNA / RNA gene outlier detection combined with siRNA cell proliferation assay identified FAM110B as a potential growth promoting key gene for CRPC. FAM110B appears to have a key role in the androgen signaling and progression of CRPC impacting multiple cancer hallmarks and therefore highlighting a potential therapeutic target. [1] Gene expression levels from 13 samples were measured using Affymetrix GeneChip Human Genome U133 plus 2.0 arrays. Sample processing and labeling were done according to the protocol provided by Affymetrix. Three micrograms of total RNA from each sample was used for the initial one-cycle cDNA synthesis. Arrays were scanned immediately after staining using a GeneChip scanner (Affymetrix). [2] aCGH was performed from 18 prostate cancer samples using 44K arrays by Agilent Technologies. Male genomic DNA (catalog number G1471, Promega, Madison, WI) was used as reference in all hybridizations. [3] Gene expression changes following FAM110B silencing in LNCaP prostate cancer cells (48 h: pooled FAM110B siRNA vs. Scrambled siRNA; 72 h: FAM110B siRNAs 1 - 4 and pooled siRNA vs. Scrambled siRNA) and ectopic FAM110B over-expression in both RWPE-1 and LNCaP cells (FAM110B-pEGFP vs. pEGFP, 48 h) were analyzed. The raw data for these Samples are available in the 'GSE28403_LNCaP_RWPE-1_Raw_Data.txt' file, which is linked to this record as a supplementary file.
2011-08-28 | E-GEOD-28403 | biostudies-arrayexpress
Project description:EZH2 is frequently over-expressed in aggressive and metastatic solid tumors, including castration resistant prostate cancer (CRPC). We sought to determine EZH2-dependent gene expression programmes in prostate cancer progression, and found an intriguing functional switch of EZH2 from a repressor to an activator during CRPC development. We used microarrays to detail the global profiling of gene expression that are differentially regulated upon EZH2 depletion in two different prostate cancer cell lines. The androgen-dependent prostate cancer cell line LNCaP and the LNCaP-derived androgen-independent cell line LNCaP-abl (abl) were used for this study, as their transcription profiles strongly resemble that of clinical androgen-dependent and castration resistant prostate tumors, respectively. EZH2 was silenced by specific siRNAs in both cell lines, and total RNA was extracted and hybridized on Affymetrix microarrays.
2012-11-30 | E-GEOD-39452 | biostudies-arrayexpress
Project description:Resistance to androgen deprivation therapies and increased androgen receptor (AR) activity are major drivers of castration-resistant prostate cancer (CRPC). Prior work has focused on targeting AR directly; however, the identification and targeting of co-activators of AR signaling remains an underexplored area. Here we demonstrate that the MLL (mixed-lineage leukemia) complex, a well-known contributor in MLL-fusion-positive leukemia, acts as a co-activator of AR signaling. AR interacts with the MLL complex via its subunit, menin. Small molecule inhibition of the menin-MLL interaction blocks AR signaling and inhibits tumor growth in vivo. Furthermore, we find that menin is up-regulated in CRPC and high expression correlates with poor overall survival. Our study identifies the MLL complex as a co-activator of AR that can be targeted in advanced prostate cancer. ASH2L / Menin / MLL1 were knocked down using shRNA /siRNA in two prostate cancer cell lines, VCaP and LNCaP.
2015-03-02 | E-GEOD-60836 | biostudies-arrayexpress
Project description:The androgen receptor (AR) is a key driver of prostate cancer (PC), even in the state of castration-resistant PC (CRPC), and frequently even after treatment with second-line hormonal therapies such as abiraterone and enzalutamide. The persistence of AR activity via both ligand-dependent and ligand-independent (including constitutively active AR splice variants) mechanisms highlights the unmet need for alternative approaches to block AR signaling in CRPC. We investigated the transcription factor GATA2 as a regulator of AR signaling and a novel therapeutic target in PC. We demonstrate that GATA2 directly promotes AR expression (both full-length and splice variant), resulting in a strong positive correlation between GATA2 and AR expression in PC (cell lines and patient specimens). Conversely, GATA2 expression is repressed by androgen and AR, suggesting a negative feedback regulatory loop that, upon androgen deprivation, derepresses GATA2 to contribute to AR overexpression in CRPC. Simultaneously, GATA2 is necessary for optimal transcriptional activity of AR (both full-length and splice variant). GATA2 co-localizes with AR and FOXA1 on chromatin to enhance recruitment of steroid receptor coactivators (SRCs) and formation of the transcriptional holocomplex. In agreement with these important functions, high GATA2 expression and transcriptional activity predicted for worse clinical outcome in PC patients. A GATA2 small molecule inhibitor suppressed the expression and transcriptional function of AR (both full-length and splice variant) and exerted potent anticancer activity against PC cell lines. We propose pharmacological inhibition of GATA2 as a “first-in-field” approach to target AR expression and function and improve outcomes in CRPC. LNCaP cells were transfected with control siRNA (3), GATA2 siRNA (3) or AR siRNA for 72 hours.
2015-01-21 | E-GEOD-63539 | biostudies-arrayexpress
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. Although initially hormone-deprovation therapy is effective to inhibit cancer progression, most of cancers relapse as castration-resistant prostate cancer (CRPC). PSF is one of RNA binding proteins associated with prostate cancer progression. In this study, we examined the effect of small molecule treatment interacting with PSF in CRPC cells. In order to investigate the effect of small molecule interacting with PSF cells, we analyzed gene expression profile in AR-positive prostate cancer cell line LNCaP and CRPC model cell derived from LNCaP cells.We treated LNCaP cells with vehicle or dihydrotestosterone (DHT) for 24 h. LTAD cells were treated with siControl or siPSF (10 nM) for 48 h. LTAD cells were treated with vehicle or small molecule interacting with PSF (No.10-3) for 48 h.
2021-05-01 | GSE155804 | GEO
Project description:siRNA mediated HDAC1 knockdown in the LNCaP prostate cancer cell line.
2021-03-01 | GSE159839 | GEO
Project description:Continued androgen receptor (AR) signaling is an established mechanism underlying castration-resistant prostate cancer (CRPC), and suppression of AR signaling remains a therapeutic goal of CRPC therapy. Constitutively active androgen receptor splicing variants (AR-Vs) lack the AR ligand-binding domain (AR-LBD), the intended target of androgen deprivation therapies (ADT) including new CRPC therapies such as abiraterone and MDV3100. While the canonical full-length AR (AR-FL) and AR-Vs are both increased in CRPC, their expression regulation, associated transcriptional programs, functional relationships, and respective roles in mediating responses to endocrine therapies have not been dissected. In this study, we show that suppression of canonical AR-FL signaling by targeting AR-LBD leads to increased AR-V expression in two cell line models of CRPC. Importantly, treatment-induced AR-Vs activate a distinct expression signature enriched for cell cycle genes without requiring the presence of AR-FL. Conversely, activation of AR-FL signaling suppresses the AR-V signature but activates expression programs mainly associated with macromolecular synthesis, metabolism, and differentiation. In prostate cancer cells and CRPC xenografts treated with MDV3100 and abiraterone, increased expression of two constitutively active AR-Vs, AR-V7 and ARV567ES, but not AR-FL, parallels increased expression of the AR-driven cell cycle gene UBE2C. In addition, protein expression of AR-V7, but not AR-FL, is positively correlated with UBE2C in clinical CRPC specimens. The cumulative in vitro and in vivo evidence support an adaptive shift toward AR-V-mediated signaling in at least a subset of CRPC tumors as the AR-LBD is rendered inactive, suggesting an important mechanism contributing to drug resistance to CRPC therapies. LNCaP cells lacking AR-V were transfected with AR-V7 with or without androgen stimulation of AR-FL (4 conditions); LNCaP95 cells expressing AR-Vs were treated with control siRNA or siRNA trageting AR-LBD or AR-DBD, with or without androgen stimulation of AR-FL (6 conditions); VCaP cells expressing AR-Vs in the presence of androgen were treated with control siRNA, siRNA trageting AR-LBD, DMSO or MDV3100 to inhibit AR-FL (4 conditions). Total 14 arrays with no replicates.
2012-03-17 | E-GEOD-36549 | biostudies-arrayexpress