Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA213679 | ENA |
REPOSITORIES: ENA
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Project description:Metastatic prostate cancer (PCa) is a terminal disease and establishment of novel therapeutic strategy specifically targeting metastasis is critically required for its management. This study was aimed at identifying metastasis-driving genes which could potentially be therapeutic targets for metastatic prostate cancer. Integrative analysis of gene expression profiles from a pair of metastatic and non-metastatic prostate cancer tissue xenografts was used to identify potential prostate cancer metastasis-driving genes. Among the candidate genes found, GATA2, a master regulator gene in the development of hematopoietic system, was particularly interesting since it is an important pioneer factor in the regulation of AR-target gene in prostate cancer. In consistent with our finding, elevated expression of the GATA2 gene in metastatic prostate cancers was found and its expression was significantly correlated with poor prognosis in prostate cancer patients. Furthermore, indication of the GATA2 gene maybe the metastasis-driving gene was evidenced in decreased of cell migration, tissue invasion and focal adhesion disassembly in GATA2-down-regulated LNCaP cells. Global gene expression analysis after silencing of the GATA2 gene revealed a significant changed in cell transcriptomes with ~ 2500 genes with > 2 fold mRNA level changed and FDR <0.05, indicates that GATA2 plays a critical role in cell reprogramming as pioneer factor in the development of prostate cancer metastasis. LNCaP human prostate cancer cells transiently knockdown with siRNA that specifically targeting GATA2 (siGATA2) or scrambled siRNA (sicontrol). RNAs were isolated from cells after 72 hours of incubation. Gene expression profiles of four biological replicates from each sample group were analyzed to identify differentially regulated downstream genes after knockdown of GATA2.
2014-01-20 | E-GEOD-49342 | biostudies-arrayexpress
Project description:Metastatic prostate cancer (PCa) is a terminal disease and establishment of novel therapeutic strategy specifically targeting metastasis is critically required for its management. This study was aimed at identifying metastasis-driving genes which could potentially be therapeutic targets for metastatic prostate cancer. Integrative analysis of gene expression profiles from a pair of metastatic and non-metastatic prostate cancer tissue xenografts was used to identify potential prostate cancer metastasis-driving genes. Among the candidate genes found, GATA2, a master regulator gene in the development of hematopoietic system, was particularly interesting since it is an important pioneer factor in the regulation of AR-target gene in prostate cancer. In consistent with our finding, elevated expression of the GATA2 gene in metastatic prostate cancers was found and its expression was significantly correlated with poor prognosis in prostate cancer patients. Furthermore, indication of the GATA2 gene maybe the metastasis-driving gene was evidenced in decreased of cell migration, tissue invasion and focal adhesion disassembly in GATA2-down-regulated LNCaP cells. Global gene expression analysis after silencing of the GATA2 gene revealed a significant changed in cell transcriptomes with ~ 2500 genes with > 2 fold mRNA level changed and FDR <0.05, indicates that GATA2 plays a critical role in cell reprogramming as pioneer factor in the development of prostate cancer metastasis.
2014-01-20 | GSE49342 | GEO
Project description:Using a bioinformatics algorithm, we screened in silico 2,650 clinically relevant drugs for a potential GATA2 inhibitor. We identified the vasodilator Dilazep as a potential GATA2 inhibitor. Dilazep exerted anticancer activity across a broad panel of PC cell lines. Global gene expression analysis revealed that dilazep suppressed the GATA2, AR, and cMyc transcriptional programs, including under CRPC conditions. We also documented suppression of cell cycle programs and decreased expression of oncogenic drivers, such as FOXM1, CENPF, EZH2, UBE2C, RRM2, as well as several mediators of metastasis, DNA damage repair and stemness. We provide, based on global gene expression analysis, proof-of-principle evidence that a small molecule can inhibit GATA2 in PC cells and can suppress its downstream AR, cMyc, and other cancer-driving effectors. We propose that GATA2 can be a therapeutic target in CRPC.
2025-03-15 | GSE147175 | GEO
Project description:Using a bioinformatics algorithm, we screened in silico 2,650 clinically relevant drugs for a potential GATA2 inhibitor. We identified the vasodilator Dilazep as a potential GATA2 inhibitor. Dilazep exerted anticancer activity across a broad panel of PC cell lines. Global gene expression analysis revealed that dilazep suppressed the GATA2, AR, and cMyc transcriptional programs, including under CRPC conditions. We also documented suppression of cell cycle programs and decreased expression of oncogenic drivers, such as FOXM1, CENPF, EZH2, UBE2C, RRM2, as well as several mediators of metastasis, DNA damage repair and stemness. We provide, based on global gene expression analysis, proof-of-principle evidence that a small molecule can inhibit GATA2 in PC cells and can suppress its downstream AR, cMyc, and other cancer-driving effectors. We propose that GATA2 can be a therapeutic target in CRPC.
2025-03-15 | GSE147215 | GEO
Project description:We investigated the role of GATA2 in prostate cancer cells beyond the AR signaling axis, and characterized the pharmacological potency of the GATA2 small molecule inhibitor (SMI) K-11706 against prostate cancer cells. K-11706, which inhibited the proliferation and invasive behavior of PC cells, and dramatically reduced the genome-wide transcriptional activity of GATA2, AR, and cMyc, leading to downregulation of several prostate cancer drivers and AR/cMyc effector genes, notably FOXM1, EZH2, and CENPF. Transcriptional profiling and functional pathway analysis of the K-11706 transcriptomic footprint against curated databases delineated a biological network composed of genes involved in cell cycle/proliferation, stemness, metastasis and DNA repair.
2025-03-15 | GSE147173 | GEO
Project description:We investigated the role of GATA2 in prostate cancer cells beyond the AR signaling axis, and characterized the pharmacological potency of the GATA2 small molecule inhibitor (SMI) K-11706 against prostate cancer cells. K-11706, which inhibited the proliferation and invasive behavior of PC cells, and dramatically reduced the genome-wide transcriptional activity of GATA2, AR, and cMyc, leading to downregulation of several prostate cancer drivers and AR/cMyc effector genes, notably FOXM1, EZH2, and CENPF. Transcriptional profiling and functional pathway analysis of the K-11706 transcriptomic footprint against curated databases delineated a biological network composed of genes involved in cell cycle/proliferation, stemness, metastasis and DNA repair.
2025-03-15 | GSE147214 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:GATA2 shRNA Expression in Castration Resistant Prostate Cancer Cell Lines
| PRJNA254050 | ENA
Project description:Genomic Signatures of Metastasis in Prostate Cancer
| PRJNA137447 | ENA
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature