Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA119769 | ENA |
REPOSITORIES: ENA
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Project description:Monoamine oxidase A (MAO-A), a mitochondrial enzyme that degrades monoamines including neurotransmitters, is highly expressed in basal cells of the normal human prostatic epithelium and in poorly differentiated (Gleason grades 4 and 5), aggressive prostate cancer (PCa). Clorgyline, an MAO-A inhibitor, induces secretory differentiation of normal prostate cells. We systematically assessed gene expression changes induced by clorgyline in E-CA cells using high-density oligonucleotide microarrays. Genes differentially expressed in treated and control cells were identified by Significance Analysis of Microarrays. Expression of genes of interest was validated by quantitative real-time polymerase chain reaction. time series design
2010-07-17 | E-GEOD-17167 | biostudies-arrayexpress
Project description:Purpose: Monoamine oxidase A (MAOA) is a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine. Its inhibitors are commonly used to treat neurologic conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostate epithelium and in high grade primary prostate cancer (PCa). Inhibition of MAOA with an irreversible inhibitor, clorgyline, induced differentiation in primary cultures of epithelial cells from normal tissues and high grade cancers. Furthermore, clorgyline treatment inhibited several oncogenic pathways in PCa cells, suggesting a clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Methods: The growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time PCR. Results: Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Conclusions: Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa. Compound Based Treatment: Clorgyline treament of VCaP cells compound_treatment_design
2010-10-25 | E-GEOD-19822 | biostudies-arrayexpress
Project description:Monoamine oxidase A (MAO-A), a mitochondrial enzyme that degrades monoamines including neurotransmitters, is highly expressed in basal cells of the normal human prostatic epithelium and in poorly differentiated (Gleason grades 4 and 5), aggressive prostate cancer (PCa). Clorgyline, an MAO-A inhibitor, induces secretory differentiation of normal prostate cells. We systematically assessed gene expression changes induced by clorgyline in E-CA cells using high-density oligonucleotide microarrays. Genes differentially expressed in treated and control cells were identified by Significance Analysis of Microarrays. Expression of genes of interest was validated by quantitative real-time polymerase chain reaction.
2010-07-17 | GSE17167 | GEO
Project description:We found that LSD1 inhibition by a monoamine oxidase inhibitor, tranylcypromine (TC), could enhance fetal gamma globin expression. Global effects of TC on erythroid expession were conducted by HG-U219 array strips.
2013-02-16 | GSE42078 | GEO
Project description:Purpose: Monoamine oxidase A (MAOA) is a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine. Its inhibitors are commonly used to treat neurologic conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostate epithelium and in high grade primary prostate cancer (PCa). Inhibition of MAOA with an irreversible inhibitor, clorgyline, induced differentiation in primary cultures of epithelial cells from normal tissues and high grade cancers. Furthermore, clorgyline treatment inhibited several oncogenic pathways in PCa cells, suggesting a clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Methods: The growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time PCR. Results: Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Conclusions: Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa. Compound Based Treatment: Clorgyline treament of VCaP cells
2010-10-25 | GSE19822 | GEO
Project description:We found that LSD1 inhibition by a monoamine oxidase inhibitor, tranylcypromine (TC), could enhance fetal gamma globin expression. Global effects of TC on erythroid expession were conducted by HG-U219 array strips. Primary human erythroid cells, which differentiated from CD34+ cells for 8 days, were harvested before or and after TC treatment (0.5 µM, 1.5 µM or 5 µM) for the gene expression analysis.
2013-02-16 | E-GEOD-42078 | biostudies-arrayexpress
Project description:Expression data from High-grade prostate cancer cells
| PRJNA192832 | ENA
Project description:Lysine-specific demethylase 1 (LSD1) is an epigenetic enzyme that oxidatively cleaves methyl groups from monomethyl and dimethyl Lys4 of histone H3 (H3K4Me1, H3K4Me2) and can contribute to gene silencing. This study describes the design and synthesis of analogs of a monoamine oxidase antidepressant, phenelzine, and their LSD1 inhibitory properties. A novel phenelzine analog (bizine) containing a phenyl-butyrylamide appendage was shown to be a potent LSD1 inhibitor in vitro and was selective versus monoamine oxidases A/B and the LSD1 homolog, LSD2. LSD1 inhibitor bizine was found to be effective at modulating bulk histone methylation in cancer cells, and ChIP-seq experiments revealed a statistically significant overlap in the H3K4 methylation pattern of genes affected by bizine and those altered in LSD1-/- cells. Treatment of two cancer cell lines, LNCaP and H460 with bizine conferred a reduction in proliferation rate, and bizine showed additive to synergistic effects on cell growth when used in combination with two out of five HDAC inhibitors tested. Moreover, neurons exposed to oxidative stress were protected by the presence of bizine, suggesting potential applications in neurodegenerative disease.
2014-11-07 | GSE55089 | GEO
Project description:Currently, comprehensive and quantitative proteomic analysis of human prostate cancer tissue specimens remains scarce, hindering the identification of protein complexes and pathways deregulated in prostate cancer. In this study, we applied TMT-SPS-MS3-based quantitative proteomics to analzye 9 normal controls, 9 low-grade prostate cancer, and 9 high-grade prostate cancer. About 3,600 proteins were quantified across all the 27 prostate specimens. Statistical analysis identified 651 proteins that are differentially expressed in high-grade prostate cancer and normal prostate. Pathway enrichment analysis revealed that the LXR/RXR activation and integrin signaling pathways are substantially downregulated in high-grade prostate cancer, compared with normal prostate cancer. In addition, protein complex analysis suggested that mitochondrial ribosomes and ribosome-biogenesis complexes are significnatly overexpressed, whereas the cholesterol effluex and focal adhesion comlexes are significantly downregulated in high-grade prostate cancer, compared with normal controls. Furthermore, differential correlation analysis indicated that the spliceosome machinery might be more active in low-grade prostate cancer, compared with normal controls. The results are expected to shed light on the molecular mechnanisms underlying the development and progression of primary prostate cancer in human patients.
2019-04-23 | PXD010744 | Pride
Project description:A comprehensive expression analysis of Wnt signaling genes was performed in a panel of prostate cancer cell lines and tissue specimens using TaqMan low density arrays. The effect of DNA methylation on gene expression was investigated using DNMT inhibitor 5-Aza-CdR. Tissue specimens from a range of disease states were used to represent the stepwise progression of prostate cancer, including benign prostatic hyperplasia (BPH), histologically benign epithelium adjacent to tumor (HB), pre-invasive high-grade prostatic intraepithelial neoplasia (HGPIN) and primary localized tumors categorized into low- and high-grade disease. Fifteen Wnt signaling related genes were idenified with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumour (r=0.76) than to BPH (r=0.57) (P<0.001). Overall, the expression profile was highly similar between tumors of high (≥7) and low (≤6) Gleason scores. Pharmacological demethylation of PC-3 cells reactivated 38 genes (≥2-fold); 40% of which inhibit Wnt signaling.
2011-11-10 | GSE33557 | GEO