PIM1 and NFATC1 targets in PC-3 prostate cancer cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA491713 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:PC-3 cells stably transfected with PIM1 overexpressing vector and transiently transfected with wt or multi-mutant NFATC1 overexpressing vector
2018-09-19 | GSE120133 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by the accumulation of myofibroblasts leading to the progressive scarring of the lung. To identify transcriptional gene programs driving persistent fibrosis in aged lungs, we performed a comparative RNA-seq analysis of fibroblasts freshly isolated from young and aged mouse lungs 30 days post-bleomycin injury. We discovered that lung fibroblasts isolated from young animals at this time point post-injury were transcriptionally similar to those isolated from uninjured mice. In contrast, aged lung fibroblasts isolated at the same time point exhibited a sustained pro-fibrotic state characterized by the elevated expression of genes implicated in inflammation, extracellular matrix remodeling, and cell survival. We identified the protein kinase pro-viral integration site of Moloney murine leukemia virus 1 (PIM1) and its direct target Nuclear Factor of Activated T Cells-1 (NFATc1) as putative drivers of the sustained profibrotic gene signatures observed in aged lung fibroblasts post-injury. PIM1 and NFATc1 transcripts were highly enriched in a pathogenic fibroblast population recently discovered in IPF lungs, and their protein expression was detected in fibroblastic foci. Overexpression of PIM1 in normal human lung fibroblasts potentiated their fibrogenic activation and this effect was dependent on NFATc1. Pharmacological inhibition of PIM1 in IPF-derived lung fibroblasts attenuated their activation and sensitized them to apoptotic stimuli. Finally, inhibition of PIM1 strongly reduced the expression of ECM remodeling and pro-survival genes and blocked the secretion of collagen in IPF lung explants ex vivo. Targeting PIM1/NFATc1 axis in pathogenic lung fibroblasts may represent a therapeutic strategy to limit their activation and promote fibrosis resolution in IPF.
2022-01-01 | GSE191208 | GEO
Project description:To identify the downstream molecules that mediate PIM1 induced aggressive prostate cancer cells, p53 and Rb-deficient mouse prostate epithelial cells were transduced with PIM1 lentivirus and performed a gene expression profile microarray.
2018-08-21 | GSE118786 | GEO
Project description:We performed the newly mapping of genome-wide NFATc1 binding events in VEGF-stimulated primary cultured endothelial cells, by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Combined NFATc1 ChIP-seq profile and the epigenetic histone marks revealed that predominant NFATc1-occupied peaks were overlapped with promoter marking but not silencer marking. DNA microarrays with NFATc1 expression or knockdown indicated the predominant NFATc1 binding targets were correlated with induced patterns. To determine NFATc1-regulated genes, a total of 5 samples were derived from human umbilical vein endothelial cells (HUVECs) stimulated with or without 50ng/mL VEGF (VEGF 60min and 0min, respectively), pretreated with cyclosporine A (VEGF 60min plus CsA) and infected with adenovirus expressing the control or constitutively active NFATc1 (Ad-control and Ad-NFATc1).
2013-09-01 | E-GEOD-49426 | biostudies-arrayexpress
Project description:We performed the newly mapping of genome-wide NFATc1 binding events in VEGF-stimulated primary cultured endothelial cells, by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Combined NFATc1 ChIP-seq profile and the epigenetic histone marks revealed that predominant NFATc1-occupied peaks were overlapped with promoter marking but not silencer marking. DNA microarrays with NFATc1 expression or knockdown indicated the predominant NFATc1 binding targets were correlated with induced patterns.
2013-09-01 | GSE49426 | GEO
Project description:Our aim was to study the effect of FGF-8 on prostate tumor growth and to identify FGF-8b-associated molecular targets in the orthotopic PC-3 nude mouse model of prostate cancer.
2008-03-04 | E-MEXP-1081 | biostudies-arrayexpress
Project description:To investigate potential molecular targets that regulate metastasis and metabolism in anoikis-resistance of prostate cancer cells, we have establised anoikis-resistant prostate PC-3 cells with ultra-low attachment 6-well plates (Corning) and employed whole genome microarray expression profiling as a discovery platform to identify differentially expressed genes between anoikis-resistant PC-3 cells and corresponding parental cells.
2020-06-26 | GSE100629 | GEO
Project description:PIM1 is an oncogenic serine/threonine kinase that promotes and maintains prostate
tumorigenesis. To more fully understand the mechanism by which PIM1 promotes oncogenesis,
we performed a chemical genetic screen to identify direct PIM1 substrates in prostate cancer
cells. To identify PIM1 substrates and their phosphorylation sites in LNCaP cells, we coupled a
chemical genetic screen with a peptide capture, mass spectrometry (MS)-based approach. We
mutated the PIM1 gatekeeper residue in the ATP binding site to accept a bulky ATP analog. By
using an ATP analog labeled with a thiol group on the gamma-phosphate, we were able specifically
label PIM1 substrates even in the presence of other cellular kinases.
2020-02-27 | MSV000085028 | MassIVE
Project description:Genome wide expression changes following 50uM Casodex treatment were investigated to determine regulatory targets commonly overlooked in gene function specific microarrays and for comparison of the effects the wild-type AR expressing PC-346C cells against the mutant androgen receptor (AR) LNCaP cell line. PC-346C Prostate Cancer cells were treated for a period of 48h with or without 50uM Casodex following a 36h seeding period. At the selected time point, total RNA was harvested from the cells for hybridization and analysis by Nimblgen Systems Inc using the homo sapiens gene expression array.
2007-09-15 | E-GEOD-8534 | biostudies-arrayexpress
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