Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA358323 | ENA |
REPOSITORIES: ENA
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Project description:Assessment of different subcellular localizations (membrane, cytosol, nucleus) of estrogen receptors by multi-epitope protein expression in 200 NSCLC specimens and matched non-cancerous tissues and ESR-1 probe mapping meta-analysis of Affymetrix 2.0 plus data in 1398 NSCLC tumors and normal lung tissues and 39 NSCLC cell lines led us to the conclusion that ERα extranuclear variants are the main ERs in NSCLC. In order to further analyze these effects we treated A549 and H520 cell lines with 17β-estradiol, 17β-estradiol-BSA (plasma membrane impermeable conjugate) and tamoxifen for 3h, in order to investigate early transcriptional effects and responsiveness to estrogen agonists and antagonists. The aim of this study was to demonstrate the functionality of NSCLC ERs and decipher which genes, canonical pathways and networks are affected by each treatment.
2016-12-22 | GSE92679 | GEO
Project description:Non-small cell lung cancer (NSCLC) is the most lethal and prevalent type of lung cancer. In almost all types of cancer, the levels of polyamines (putrescine, spermidine, and spermine) are increased, playing a pivotal role in tumor proliferation. Indomethacin, a non-steroidal anti-inflammatory drug, increases the abundance of an enzyme termed spermidine/spermine-N1-acetyltransferase (SSAT) encoded by the SAT1 gene. This enzyme is a key player in the export of polyamines from the cell. The aim of this study was to compare the effect of indomethacin on two NSCLC cell lines, and their combinatory potential with polyamine-inhibitor drugs in NSCLC cell lines. A549 and H1299 NSCLC cells were exposed to indomethacin and evaluations included SAT1 expression, SSAT levels, and the metabolic status of cells. Moreover, the difference in polyamine synthesis enzymes among these cell lines as well as the synergistic effect of indomethacin and chemical inhibitors of the polyamine pathway enzymes on cell viability were investigated. Indomethacin increased the expression of SAT1 and levels of SSAT in both cell lines. In A549 cells, it significantly reduced the levels of putrescine and spermidine. However, in H1299 cells, the impact of treatment on the polyamine pathway was insignificant. Also, the metabolic features upstream of the polyamine pathway (i.e., ornithine and methionine) were increased. In A549 cells, the increase of ornithine correlated with the increase of several metabolites involved in the urea cycle. Evaluation of the levels of the polyamine synthesis enzymes showed that ornithine decarboxylase is increased in A549 cells, whereas S-adenosylmethionine-decarboxylase and polyamine oxidase are increased in H1299 cells. This observation correlated with relative resistance to polyamine synthesis inhibitors eflornithine and SAM486 (inhibitors of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, respectively), and MDL72527 (inhibitor of polyamine oxidase and spermine oxidase). Finally, indomethacin demonstrated a synergistic effect with MDL72527 in A549 cells and SAM486 in H1299 cells. Collectively, these results indicate that indomethacin alters polyamine metabolism in NSCLC cells and enhances the effect of polyamine synthesis inhibitors, such as MDL72527 or SAM486. However, this effect varies depending on the basal metabolic fingerprint of each type of cancer cell.
2021-02-08 | MTBLS873 | MetaboLights
Project description:We respectively knocked down ZNF200 and DDX17 in the H520 and A549 cell lines. Since H3K4me3 is an epigenetic modification that marks the active state of gene promoter regions and is typically associated with the activation of gene expression, we subsequently performed ATAC-seq experiments using antibodies against histone H3K4me3.
2026-02-26 | GSE308112 | GEO
Project description:In order to explore the molecular mechanism of ZNF200 in the development of NSCLC, we conducted CUT&Tag experiments in the H1299 cell line using IgG and ZNF200 antibodies. Based on previous exploratory experiments, we found an interaction between DDX17 and ZNF200. Therefore, we stably transfected DDX17-HA into H1299 cells and performed CUT&Tag experiments using IgG and ZNF200 antibodies. We then discovered that both ZNF200 and DDX17 act on the promoter region of RBP-J. Consequently, in the DDX17-HA stable transfectants of H1299,H520 and A549 cells, we knocked down ZNF200 and performed CUT&Tag experiments using HA antibodies. At the same time, we knocked down ZNF200 and DDX17 in the H520and A549 cell lines, respectively. Since H3K4me3, as an epigenetic modification, is a hallmark of the active status of gene promoter regions and is usually associated with the activation of gene expression, we subsequently used antibodies against histone H3K4me3 for the CUT&Tag experiments.
2026-02-26 | GSE309203 | GEO
Project description:Rationale: Tamoxifen prevents the recurrence of breast cancer and is also beneficial against bone demineralization and arterial diseases, as it acts as an Estrogen Receptor (ER) α antagonist in ER-positive breast cancers, whereas it mimics the protective action of 17β-estradiol (E2) in other tissues such as arteries. However, the mechanisms of these tissue-specific actions remain unclear. Objective: Here we tested whether tamoxifen is able to accelerate endothelial healing and analyzed the underlying mechanisms. Methods and Results: Using three complementary mouse models of carotid artery injury, we demonstrated that both tamoxifen and estradiol accelerated endothelial healing, but only tamoxifen required the presence of the underlying medial smooth muscle cells. Chronic treatment with E2 and tamoxifen elicited differential gene expression profiles in the carotid artery. The use of transgenic models mouse targeting either whole ERα in a cell-specific manner or ERα subfunctions (membrane/extra-nuclear versus genomic/transcriptional) demonstrated that E2-induced acceleration of endothelial healing is mediated by membrane ERα in endothelial cells, while the effect of tamoxifen is mediated by the nuclear actions of ERα in smooth muscle cells. Conclusion: Whereas tamoxifen acts as an anti-estrogen and ERα antagonist in breast cancer, but also on the membrane ERα of endothelial cells, it accelerates endothelial healing through activation of nuclear ERα in smooth muscle cells, inviting to revisit the mechanisms of action of selective modulation of ERα.
2023-04-12 | GSE154268 | GEO
Project description:The receptor tyrosine kinase (RTK) EGFR is overexpressed and mutated in NSCLC. These mutations can be targeted by RTK inhibitors (TKIs), such as erlotinib. Chromatin-modifying agents offer a novel therapy approach by sensitizing tumor cells to TKIs. The NSCLC cell lines HCC827 (EGFR mutant, adenocarcinoma), A549 (EGFR wt, adenocarcinoma) and NCI-H460 (EGFR wt, large cell carcinoma) were analyzed by SNP6.0 array. Changes in proliferation were quantified by WST-1 assay, apoptosis by Annexin V/7-AAD flow cytometry and histone marks (acH3, H3K4me1,-2,-3) by immunoblotting. Expectedly, the EGFR wt cell lines A549 and NCI-H460 were insensitive to the growth-inhibiting effect of single-agent erlotinib (IC50 70-100µM), compared to HCC827 (IC50 <0.02μM). Treatment with panobinostat diminished growth to <50% in both EGFR wt and <30% in HCC827 cells. The combination of both drugs significantly reduced proliferation by ≥70% in A549, >95% in HCC827, but not further in NCI-H460. Panobinostat alone induced differentiation and expression of p21WAF1/CIP1 and p53 in all three cell lines, with almost no further increase when combined with erlotinib. In contrast, combination treatment additively decreased pERK, pAKT and pEGFR in A549, and synergistically induced acH3 in both adenocarcinoma lines. Surprisingly, we also saw an induction of H3K4 methylation marks in all three cell lines. In conclusion, panobinostat synergistically sensitized lung adenocarcinoma cells to the antiproliferative effects of erlotinib. Since single-agent erlotinib has only modest clinical effects in adenocarcinoma EGFR wt patients, combination therapy with an HDACi might offer a promising therapy approach to extend this activity. Copy-number analysis of three NSCLC cell lines HCC827, A549 and NCI-H460 (in unicates) was performed according to protocol by Affymetrix Genome-Wide Human SNP-Array 6.0.
2014-12-03 | E-GEOD-63784 | biostudies-arrayexpress
Project description:Extracts from the rhizome of Cimicifuga racemosa (black cohosh) are increasingly popular as herbal alternative to hormone replacement therapy (HRT) for the alleviation of postmenopausal disorders. However, the molecular mode of action and the active principles are presently not clear. Previously published data have been largely contradictory. We, therefore, investigated the effects of a lipophilic Cimicifuga rhizome extract on the ER+ breast cancer MCF-7 cells at transcriptional level in comparision to 17beta-estradiol and the ER antagonist tamoxifen. With the extract 431 genes were regulated more than 1.5 fold. The overall expression pattern differed from those of 17β-estradiol or the estrogen receptor antagonist tamoxifen. We observed an enrichment of genes in an anti-proliferative and apoptosis-sensitizing manner, together with an increase of mRNAs coding for gene products involved in several stress response pathways. Regulated genes of these functional groups were highly overrepresented among all regulated genes. Various transcripts coding for oxidoreductases were induced, as for example the cytochrome P450 family members 1A1 and 1B1. In addition, some transcripts associated with antitumor but also tumor-promoting activity were regulated. Keywords: treatment with black cohosh
2007-09-28 | GSE6800 | GEO
Project description:Although estrogenic compounds promise therapeutic potential in treating various conditions, concerns regarding their endocrine-disrupting effects have been raised Current methodologies for screening estrogenicity in rodent models are limited to the female-specific uterotrophic bioassay. Studies have reported enlargement of seminal vesicles in orchiectomized males treated with estrogens. However, identifying estrogenicity strictly through changes in wet weights is uninformative regarding the molecular mechanisms of these agents. Therefore, protein-based biomarkers can complement and improve the sensitivity of the weight-based assessments. To this end, we present a discovery-driven proteomic analysis on 17β-estradiol's effects on the seminal vesicles. We treated orchidectomized mice with the hormone for five days, and used the vehicle-treated group as control. Differentially expressed proteins in the seminal vesicles between the two groups were identified through label-free quantification using data-dependent nanoflow liquid chromatography–tandem mass spectrometry. We identified 668 total proteins, of which 133 were found to be regulated significantly by 17β-estradiol. Ingenuity Pathway Analysis® linked them to several hormone-affected pathways, including those associated with immune function such as neutrophil degranulation. The altered protein interaction networks were also related to functions, including endocrine disruption, abnormal metabolism, and therapeutic effects. Overall, we identified several potential biomarkers for estrogenicity in the mouse seminal vesicles including those not previously linked with exogenous 17β-estradiol exposure such as spondin-1
2025-05-07 | PXD056329 | Pride
Project description:Illumina miRNA-seq method to uncover the expression profile of NSCLC in-vitro experimental models consisting of cell lines A549, H460 compared to healthy BEAS-2B cell line, and lung tissue (NSCLC and paired normal) from urethane treated 6-week-old FVB/NJ mice. We aimed to uncover the divergent epigenetic background of KRAS-mutant NSCLC in mouse and human cell lines, extensively used as biological models in relevant research. To that end, we have comprehensively mapped the functional miRNA and lncRNA landscape of human (A549 and H460) and mouse (experimentally developed LUAD) NSCLC models and correlated current results with LRF/ZBTB7A expression
2023-12-25 | GSE251697 | GEO
Project description:Studies of gene expression profiles using the whole genomewide microarray analysis of miRNA in SUM149PT cells (ER-, p53mut) and SUM190PT cells (ER-, p53mut) when treated with 5-7.5 µM CG-1521 alone and in combination with 10 nM 17β-Estradiol. Comparisons between each treatment group provides evidence for the dysregulation of miRNA affecting genes associated with the spindle assembly checkpoint. Four independent experiments were carried out in SUM149PT and SUM190PT cells, which were treated with vehicle (ethanol/DMSO), 10nM 17β-Estradiol, 5 or 7.5µM CG-1521, and the combination of 17β-Estradiol and CG-1521. Total RNA was extracted from cell lysates using QIAGEN miRNeasy mini kit after 48h of treatment.
2011-04-12 | E-GEOD-28543 | biostudies-arrayexpress