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Transcriptional analysis of the effect of monoamine oxidase A (MAOA) in human prostate cancer enzalutamide (ENZ)-resistant C4-2B (C4-2B ENZR) and LNCaP cells

ABSTRACT: The overall goal of this study was to compare gene expression profiles in control and MAOA-knockdown prostate cancer cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161691 | GEO | 2020/11/19

REPOSITORIES: GEO

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Transcriptional analysis of the effect of monoamine oxidase A (MAOA) in human prostate cancer enzalutamide (ENZ)-resistant C4-2B (C4-2B ENZR) and LNCaP cells

Project description:Transcriptional analysis of the effect of monoamine oxidase A (MAOA) in human prostate cancer enzalutamide (ENZ)-resistant C4-2B (C4-2B ENZR) and LNCaP cells

| PRJNA679169 | ENA

Expression data from prostate cancer cell lines C4-2B (enzalutamide sensitive) and C4-2B-MDVR (enzalutamide resistant) cells

Project description:Prostate cancer C4-2B cells were cultured in enzalutamide in a dose-escalation manner. After sixty passages cells were resistant to enzalutamide, with a specific sets of genes been deregulated. We performed global gene expression analysis by cDNA microarrays to identify genes responsible for enzalutamide resistance in C4-2B-MDVR cells. Enzalutamide resistant C4-2B-MDVR cells were selected from C4-2B cells during long time enzalutamide treatment. Genes responsible for enzalutamide resistance were identified using C4-2B vs. C4-2B-MDVR RNA extraction and hybridization on Affymetrix microarrays.

2015-04-09 | E-GEOD-64143 | biostudies-arrayexpress

Expression data from prostate cancer cell lines C4-2B (enzalutamide sensitive) and C4-2B-MDVR (enzalutamide resistant) cells

2015-04-09 | GSE64143 | GEO

Effect of Monoamine oxidase A (MAOA) inhibitors on androgen-sensitive and castration-resistant prostate cancer cells.

Project description:BACKGROUND:Monoamine oxidase A (MAOA) is best known for its role in neuro-transmitter regulation. Monoamine oxidase inhibitors are used to treat atypical depression. MAOA is highly expressed in high grade prostate cancer and modulates tumorigenesis and progression in prostate cancer. Here, we investigated the potential role of MAOA inhibitors (MAOAIs) in relation to the androgen receptor (AR) pathway and resistance to antiandrogen treatment in prostate cancer. METHODS:We examined MAOA expression and the effect of MAOI treatment in relation to AR-targeted treatments using the LNCaP, C4-2B, and 22Rv1 human prostate cancer cell lines. MAOA, AR-full length (AR-FL), AR splice variant 7 (AR-V7), and PSA expression was evaluated in the presence of MAOAIs (clorgyline, phenelzine), androgenic ligand (R1881), and antiandrogen (enzalutamide) treatments. An enzalutamide resistance cell line was generated to test the effect of MAOAI treatment in this model. RESULTS:We observed that MAOAIs, particularly clorgyline and phenelzine, were effective at decreasing MAOA activity in human prostate cancer cells. MAOAIs significantly decreased growth of LNCaP, C4-2B, and 22Rv1 cells and produced additive growth inhibitory effects when combined with enzalutamide. Clorgyline decreased expression of AR-FL and AR-V7 in 22Rv1 cells and was effective at decreasing growth of an enzalutamide-resistant C4-2B cell line with increased AR-V7 expression. CONCLUSIONS:MAOAIs decrease growth and proliferation of androgen-sensitive and castration-resistant prostate cancer cells. Clorgyline, in particular, decreases expression of AR-FL and AR-V7 expression and decreases growth of an enzalutamide-resistant cell line. These findings provide preclinical validation of MAOA inhibitors either alone or in combination with antiandrogens for therapeutic intent in patients with advanced forms of prostate cancer.

| S-EPMC7462252 | biostudies-literature

Transcriptome analysis of Enzalutamide-resistant C4-2B (C4-2B MDVR) cells treated with Indocin.

Project description:The overall goal of this study was to identify genes that were differentially-expressed in C4-2B MDVR cells treated with Indocin. C4-2B MDVR were either treated with Indocin (20 uM) or DMSO vehicle control for 3 days, followed by isolation of total cellular RNA. Transcriptome analysis was performed with RNA-Sequencing (RNA-Seq) in order to identify differentially-expressed genes (DEGs) induced by Indocin treatment.

2019-09-29 | GSE129596 | GEO

Comparative genomic and transcriptomic analyses of LNCaP and C4-2B prostate cancer cell lines.

Project description:The LNCaP and C4-2B cell lines form an excellent preclinical model to study the development of metastatic castration-resistant prostate cancer, since C4-2B cells were derived from a bone metastasis that grew in nude mice after inoculation with the LNCaP-derived, castration-resistant C4-2 cells. Exome sequencing detected 2188 and 3840 mutations in LNCaP and C4-2B cells, respectively, of which 1784 were found in both cell lines. Surprisingly, the parental LNCaP cells have over 400 mutations that were not found in the C4-2B genome. More than half of the mutations found in the exomes were confirmed by analyzing the RNA-seq data, and we observed that the expressed genes are more prone to mutations than non-expressed genes. The transcriptomes also revealed that 457 genes show increased expression and 246 genes show decreased expression in C4-2B compared to LNCaP cells. By combining the list of C4-2B-specific mutations with the list of differentially expressed genes, we detected important changes in the focal adhesion and ECM-receptor interaction pathways. Integration of these pathways converges on the myosin light chain kinase gene (MLCK) which might contribute to the metastatic potential of C4-2B cells. In conclusion, we provide extensive databases for mutated genes and differentially expressed genes in the LNCaP and C4-2B prostate cancer cell lines. These can be useful for other researchers using these cell models.

| S-EPMC3938550 | biostudies-literature

A Neurogenic Signature Involving Monoamine Oxidase-A Controls Human Thermogenic Adipose Tissue Development

Project description:Mechanisms that control “beige/brite” thermogenic adipose tissue development may be harnessed to improve human metabolic health. To define these mechanisms, we developed a species-hybrid model in which human mesenchymal progenitor cells were used to develop white or thermogenic/beige adipose tissue in mice. The hybrid adipose tissue developed distinctive features of human adipose tissue, such as larger adipocyte size, despite its neurovascular architecture being entirely of murine origin. Thermogenic adipose tissue recruited a denser, qualitatively distinct vascular network, differing in genes mapping to circadian rhythm pathways, and denser sympathetic innervation. The enhanced thermogenic neurovascular network was associated with human adipocyte expression of THBS4, TNC, NTRK3 and SPARCL1, which enhance neurogenesis, and decreased expression of MAOA and ACHE, which control neurotransmitter tone. Systemic inhibition of MAOA, which is present in human but absent in mouse adipocytes, induced browning of human but not mouse adipose tissue, revealing the physiological relevance of this pathway. Our results reveal species-specific cell type dependencies controlling the development of thermogenic adipose tissue and point to human adipocyte MAOA as a potential target for metabolic disease therapy.

2022-09-27 | GSE200141 | GEO

Transcriptome analysis of enzalutamide-sensitive and -resistant C4-2B cells

Project description:The overall goal of this study was to identify genes differentially expressed in enzalutamide-sensitive (C4-2B Con) and enzalutamide-resistant (C4-2B ENZR) C4-2B cells.

2020-10-20 | GSE159548 | GEO

High-throughput profiling of mRNA from parental and Enzalutamide resistant C4-2b prostate cancer cell lines

Project description:We established an enzalutamide-resistant C4-2b prostate cell line that has an active androgen receptor by maintaining the C4-2b cell line in serially increasing concentrations of enzalutamide. Among the CRPC cell lines, we selected the C4-2b cell line because it is known to have AR variants, and we desired to identify enzymes with the ability to regulate the activity of AR variants as well as the wild type AR. After 2 months, we acquired resistant cells in even 10 uM enzalutamide. After validation of enzalutamide-resistant character, we analyzed global changes in mRNA expression by using quantitative mRNA-sequencing analysis.

2020-02-01 | GSE110802 | GEO

Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping

Project description:Monoamine oxidases MAOA and MAOB catalyze important cellular functions such as the deamination of neurotransmitters. Correspondingly, MAO inhibitors are used for the treatment of severe neuropsychiatric disorders such as depression. A commonly prescribed drug against refractory depression is tranylcypromine, however, the side effects are poorly understood. In order to decipher putative off-targets, we synthesized two tranylcypromine probes equipped with either an alkyne moiety or an alkyne-diazirine minimal photocrosslinker for in situ proteome profiling. Surprisingly, LC-MS/MS analysis revealed low enrichment of MAOA and relatively promiscuous labeling of proteins. Photoprobe labeling paired with fluorescent imaging studies revealed lysosomal trapping which could be largely reverted by the addition of lysosomotropic drugs.

2020-10-20 | PXD018580 | Pride

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