Characterization of AR interactome in prostate cancer cells after MC3324 treatment
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Epithelial Cell, Prostate Cancer Cell Line
DISEASE(S): Prostate Adenocarcinoma
SUBMITTER: 
Tommaso De Marchi
LAB HEAD: Lucia Altucci
PROVIDER: PXD029249 | Pride | 2022-10-13
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| 20190503_FASTA_hs_CnI.fasta | Fasta | |||
| TDM_P1907_260.raw | Raw | |||
| TDM_P1907_261.raw | Raw | |||
| TDM_P1907_262.raw | Raw | |||
| TDM_P1907_264.raw | Raw |
Items per page: 5 1 - 5 of 31 |
Publications
Histone lysine demethylase inhibition reprograms prostate cancer metabolism and mechanics.
Chianese Ugo U Papulino Chiara C Passaro Eugenia E Evers Tom Mj TM Babaei Mehrad M Toraldo Antonella A De Marchi Tommaso T Niméus Emma E Carafa Vincenzo V Nicoletti Maria Maddalena MM Del Gaudio Nunzio N Iaccarino Nunzia N Randazzo Antonio A Rotili Dante D Mai Antonello A Cappabianca Salvatore S Mashaghi Alireza A Ciardiello Fortunato F Altucci Lucia L Benedetti Rosaria R
Molecular metabolism 20220806
<h4>Objective</h4>Aberrant activity of androgen receptor (AR) is the primary cause underlying development and progression of prostate cancer (PCa) and castration-resistant PCa (CRPC). Androgen signaling regulates gene transcription and lipid metabolism, facilitating tumor growth and therapy resistance in early and advanced PCa. Although direct AR signaling inhibitors exist, AR expression and function can also be epigenetically regulated. Specifically, lysine (K)-specific demethylases (KDMs), whi ...[more]
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Project description:These proteomic data were produced in order to assess the effect of drug 3324, a pan-lysine demethylase inhibitor, on the estrogen receptor (ER) and Lysine Demethylase1 (LSD1)protein interaction networks.
2021-09-08 | PXD012781 | Pride
Project description:The RNA-binding protein AU-rich-element factor-1 (AUF-1) regulates mRNA decay and translation of genes during inflammation and cellular senescence, two pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). Decreased AUF-1 expression was described in bronchiolar epithelium of COPD patients versus controls and in vitro cytokine-challenged airway epithelial cells, prompting the identification of epithelial AUF-1-targeted transcripts and function. RNA immunoprecipitation-sequencing (RIP-Seq) identified, in the human BEAS-2B cell line, 494 AUF-1-bound mRNAs enriched in their 3’-untranslated regions for a Guanine-Cytosine (GC)-rich binding motif, selectively confirmed by biotin pulldown. AUF-1-targets’ steady-state levels were equally affected by partial or near-total AUF-1 loss induced by cytomix (TNF/IL1/IFN/10 nM each) and siRNA, respectively, with differential transcript decay rates. Cytomix-decreased AUF-1 levels in BEAS-2B and primary human small-airways epithelium (HSAEC) associated with cell-cycle arrest, increased lysosomal damage and senescence-associated secretory phenotype (SASP) factors and with increased AUF-1 in extracellular vesicles. In-silico analysis found enriched AUF-1-targets in COPD-related pathways, SASP proteome atlas, transcriptomic COPD databases of HSAEC, lung tissue and single-cell RNA-sequencing. Intracellular and exosomal-associated AUF-1 may mediate airway epithelial inflammatory responses.
2023-04-14 | E-MTAB-12583 | biostudies-arrayexpress
Project description:The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptorârelated orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an ARâROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa. A total of 16 samples were analyzed in this study. The study included one cell line C4-2B. C4-2B cells were cultured in medium containing vehicle control or SR2211 (5 µM) for 24 hours, cells then were collected for ChIP seq assay
2016-03-08 | E-GEOD-72714 | biostudies-arrayexpress
Project description:The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptorârelated orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an ARâROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa. A total of 6 samples were analyzed in this study. The study included one cell line C4-2B. C4-2B cells were cultured in medium containing vehicle control and/or SR2211 and/or XY011 and/or Enzalutamide (ENZ). The untreated C4-2B cells served as controls for the study.
2016-03-08 | E-GEOD-72483 | biostudies-arrayexpress
Project description:The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature (“Core” OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis. Keywords: cancer, transcription-profile, bone, metastasis, stroma 3 samples of VCaP xenografted mouse bones (VCaP xenografts 1/2/3), 3 samples of C4-2B xenografted mouse bones (C4-2B xenografts 1/2/3), 2 samples of Ep156T xenografted mouse bones (Ep156T xenografts 1/2), 2 samples of sham-operated mouse bones (sham-operated bones 1/2) and 3 samples of intact mouse bones (intact bones 1/2/3) were profiled on Affymetrix Mouse Genome 430A 2.0 Arrays. Sample code: MVX stands for VCaP xenografts, MBM for Intact bone samples, MCX for C4-2B xenografts and MNX for Sham-operated bones samples
2014-12-09 | E-GEOD-22813 | biostudies-arrayexpress
Project description:This study aimed to further our understanding of the role that hypermethylatioted in cancer 1 (HIC1) plays in prostate cancer (PCa) development. Microarrays were searched for some genes that had correlated expression with HIC1 mRNA. Our data showed that HIC1 promoter hypermethylation was presented in cell lines, tissues and plasma of PCa patients. According to fold-change screening between restoring expression of HIC1 and its respective control cells, both up-regulated and down-regulated genes were commonly observed in PC3 and C4-2B cells. The restoring expression HIC1 in PCa lines were respectively noted as PC3-HIC1 and C4-2B-HIC1 cells, and the respective controls were noted as C4-2B-GFP and PC3-GFP cells.
2012-11-17 | E-GEOD-42336 | biostudies-arrayexpress
Project description:Expression profiling of isoflavone and 3,3’-diindolylmethane treated C4-2B prostate cancer cells was conducted using Affymetrix Human Genome U133 Plus 2.0. Array C4-2B prostate cancer cells were treated with isoflavone and B-DIM for 6 hours or longer up to 72 hours. Gene expression profiling was conducted
2012-01-25 | E-GEOD-35324 | biostudies-arrayexpress
Project description:We identified a novel lipogenic gene, ELOVL7, as an over-expressed gene in prostate cancer (PC) cells and it is involved in elongation of long-chain fatty acids and can play some important roles in prostate carcinogenesis. To investigate into downstream pathways of ELOVL7, we performed the gene expression analysis by the genome-wide cDNA microarrays. The genome–wide gene expression patterns were compared between PC cells transfected with siELOVL7 and these with siCONTROL and between the ELOVL7-overexpressing in-vivo tumors in mice bread with high fat diet (HFD) and those with normal diet (ND). HFD treatment significantly promoted the growth of ELOVL7-overexpressed PC cells in vivo. As a result, we identified five genes (IER3, HDAC8, GDF15, UGT2B11, and S1PR3) whose expressions were down-regulated with 20% and more in ELOVL7 knockdown and also were up-regulated with 20% and more in the tumors in the mice bread with HFD. The genome–wide gene expression patterns were compared between PC cells transfected with siELOVL7 and these with siCONTROL and between the ELOVL7-overexpressing in-vivo tumors bread with high fat diet (HFD) and those with normal diet (ND). HFD treatment significantly promoted the growth of ELOVL7-overexpressed PC cells in vivo. The competitive hybridization was performed three times for each comparison (siELOVL7-1, -2, and-3; HFD-1, -2, and -3).
2009-04-01 | E-GEOD-14852 | biostudies-arrayexpress
Project description:To define the signalling of extracellular GTP as enhancer of myogenesis, we investigated if the gene expression profile of differentiated C2C12 cells (4 and 24 hours in SM) was affected by extracellular GTP. Two-condition experiment, GTP-treated C2C12 cells vs Control C2C12 cells at 4 h and 24 h of differentiation. Biological replicates: 1 control, 1 GTP-treated cells, independently grown and harvested. One replicate per array.
2010-06-20 | E-GEOD-18531 | biostudies-arrayexpress
Project description:Background: Prostate cancer (PCa) cells preferentially metastasize to bone at least in part by acquiring osteomimetic properties. Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome-wide mRNA expression changes in PCa cells in response to Runx2. Results: We engineered a C4-2B PCa sub-line called C4-2B/Rx2dox, in which doxycycline (Dox) treatment stimulates Runx2 expression from very low levels to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer-associated functions. They included secreted factors (CSF2, SDF-1), proteolytic enzymes (MMP9, CST7), cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A), intracellular signaling molecules (DUSP1, SPHK1, RASD1) and transcription factors (Sox9, SNAI2, SMAD3) functioning in epithelium to mesenchyme transition (EMT), tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels declined after Dox withdrawal. Conclusions: The effects of Runx2 in C4-2B/Rx2dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is therefore an attractive target for the development of novel diagnostic, prognostic and therapeutic approaches to PCa management. Targeting Runx2 may prove more effective than focusing on its individual downstream genes and pathways. C4-2B/Rx2dox cells were subjected to microarray gene expression analysis after one and two days of treatment with either Dox or vehicle in biological quadruplicates (a total of 16 samples).
2010-12-26 | E-GEOD-24261 | biostudies-arrayexpress