Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA225520 | ENA |
REPOSITORIES: ENA
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Project description:Epithelial-mesenchymal transition (EMT) has recently been recognized as a key element of cell invasion, migration, metastasis, and drug resistance in several types of cancer, including non-small cell lung cancer (NSCLC). Our aim was to clarify microRNA (miRNA) -related mechanisms underlying EMT followed by acquired resistance to epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) in NSCLC. MiRNA expression profiles were examined before and after transforming growth factor-beta1 (TGF-M-NM-21) exposure in four human adenocarcinoma cell lines with or without EMT. Correlation between expressions of EMT-related miRNAs and resistance to EGFR-TKI gefitinib was evaluated. MiRNA array and quantitative RT-PCR revealed that TGF-M-NM-21 significantly induced overexpression of miR-134, miR-487b, and miR-655, which belong to the same cluster located on chromosome 14q32, in lung adenocarcinoma cells with EMT. MAGI2 (membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2), a predicted target of these miRNAs and a scaffold protein required for PTEN (phosphatase and tensin homolog), was diminished in A549 cells with EMT after the TGF-M-NM-21 stimulation. Overexpression of miR-134 and miR-487b promoted the EMT phenomenon and affected the drug resistance to gefitinib, whereas knockdown of these miRNAs inhibited the EMT process and reversed TGF-M-NM-21-induced resistance to gefitinib. Our study demonstrated that the miR-134/487b/655 cluster contributed to the TGF-M-NM-21-induced EMT phenomenon and affected the resistance to gefitinib by directly targeting MAGI2, whose suppression subsequently caused loss of PTEN stability in lung cancer cells. The miR-134/miR-487b/miR-655 cluster may be new therapeutic targets in advanced lung adenocarcinoma patients, depending on the EMT phenomenon. miRNA expression profiles before and after TGF-M-NM-21 exposure were assessed in the four lung adenocarcinoma cell lines, A549, LC2/ad, PC3, and, PC9 by TaqMan miRNA arrays. Relative ratios of miRNAs in cells after TGF-M-NM-21 exposure were calculated when compared with the cells before TGF-M-NM-21 exposure.
2013-10-30 | E-GEOD-51828 | biostudies-arrayexpress
Project description:Epithelial-mesenchymal transition (EMT) has recently been recognized as a key element of cell invasion, migration, metastasis, and drug resistance in several types of cancer, including non-small cell lung cancer (NSCLC). Our aim was to clarify microRNA (miRNA) -related mechanisms underlying EMT followed by acquired resistance to epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) in NSCLC. MiRNA expression profiles were examined before and after transforming growth factor-beta1 (TGF-β1) exposure in four human adenocarcinoma cell lines with or without EMT. Correlation between expressions of EMT-related miRNAs and resistance to EGFR-TKI gefitinib was evaluated. MiRNA array and quantitative RT-PCR revealed that TGF-β1 significantly induced overexpression of miR-134, miR-487b, and miR-655, which belong to the same cluster located on chromosome 14q32, in lung adenocarcinoma cells with EMT. MAGI2 (membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2), a predicted target of these miRNAs and a scaffold protein required for PTEN (phosphatase and tensin homolog), was diminished in A549 cells with EMT after the TGF-β1 stimulation. Overexpression of miR-134 and miR-487b promoted the EMT phenomenon and affected the drug resistance to gefitinib, whereas knockdown of these miRNAs inhibited the EMT process and reversed TGF-β1-induced resistance to gefitinib. Our study demonstrated that the miR-134/487b/655 cluster contributed to the TGF-β1-induced EMT phenomenon and affected the resistance to gefitinib by directly targeting MAGI2, whose suppression subsequently caused loss of PTEN stability in lung cancer cells. The miR-134/miR-487b/miR-655 cluster may be new therapeutic targets in advanced lung adenocarcinoma patients, depending on the EMT phenomenon.
2013-10-30 | GSE51828 | GEO
Project description:The model is based on publication:
Mathematical analysis of gefitinib resistance of lung adenocarcinoma caused by MET amplification
Abstract:
Gefitinib, one of the tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR), is effective for treating lung adenocarcinoma harboring EGFR mutation; but later, most cases acquire a resistance to gefitinib. One of the mechanisms conferring gefitinib resistance to lung adenocarcinoma is the amplification of the MET gene, which is observed in 5–22% of gefitinib-resistant tumors. A previous study suggested that MET amplification could cause gefitinib resistance by driving ErbB3-dependent activation of the PI3K pathway. In this study, we built a mathematical model of gefitinib resistance caused by MET amplification using lung adenocarcinoma HCC827-GR (gefitinib resistant) cells. The molecular reactions involved in gefitinib resistance consisted of dimerization and phosphorylation of three molecules, EGFR, ErbB3, and MET were described by a series of ordinary differential equations. To perform a computer simulation, we quantified each molecule on the cell surface using flow cytometry and estimated unknown parameters by dimensional analysis. Our simulation showed that the number of active ErbB3 molecules is around a hundred-fold smaller than that of active MET molecules. Limited contribution of ErbB3 in gefitinib resistance by MET amplification is also demonstrated using HCC827-GR cells in culture experiments. Our mathematical model provides a quantitative understanding of the molecular reactions underlying drug resistance.
2019-09-30 | BIOMD0000000827 | BioModels
Project description:TGF-beta treatment of Panc-1 pancreatic adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments. The goal of the experiment is to profile temporal gene expression changes during TGF-beta-induced epithelial-mesenchymal transition (EMT). During EMT cancer cells lose their epithelial specifc proteins and gain mesenchymal proteins to acquire migratory and invasive phenotype essential for metastasis. Human Panc-1 pancreatic adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 48 h to induce EMT. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques. Human Panc-1 pancreatic adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 48 h. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques.
2010-09-03 | E-GEOD-23952 | biostudies-arrayexpress
Project description:TGF-beta treatment of Panc-1 pancreatic adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments. The goal of the experiment is to profile temporal gene expression changes during TGF-beta-induced epithelial-mesenchymal transition (EMT). During EMT cancer cells lose their epithelial specifc proteins and gain mesenchymal proteins to acquire migratory and invasive phenotype essential for metastasis. Human Panc-1 pancreatic adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 48 h to induce EMT. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques.
2010-09-03 | GSE23952 | GEO
Project description:Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) facilitate breast cancer (BC) metastasis, however stable molecular changes that result as a consequence of these processes remain poorly defined. Therefore, we sought to identify molecular markers that could distinguish tumor cells that had completed the EMT:MET cycle in the hopes of identifying and targeting unique aspects of metastatic tumor outgrowth.Therefore, normal murine mammary gland (NMumG) cells transformed by overexpression of EGFR (NME) cells were cultured in the presence of TGF-beta1 (5 ng/ml) for 4 weeks, at which point TGF-beta1 supplementation was discontinued and the cells were allowed to recover for an additional 4 weeks (Post-TGF-Rec). Total RNA was prepared from unstimulated cells (Pre-TGF) of similar passage and compared by microarray analysis. The two groups were analyzed in triplicate, three Pre-TGF samples and three Post-TGF-Rec samples.
2014-01-30 | E-GEOD-54491 | biostudies-arrayexpress
Project description:Time Course of TGF-beta treatment of A549 lung adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments. The goal of the experiment is to profile temporal gene expression changes during TGF-beta-induced epithelial-mesenchymal transition (EMT). During EMT cancer cells loose their epithelial specifc proteins and gain mesenchymal proteins to acquire migratory and invasive phenotype essential for metastasis. Human A549 lung adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 h to induce EMT. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques. We provide the raw .CEL files and a supplementary Excel spreadsheet with log-transformed data and selected results from a statistical analysis. Experiment Overall Design: Human A549 lung adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 h. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques. The 2 h sample of the third experiment was not run on an array due to poor RNA, so that only 26 arrays were run.
2009-09-15 | E-GEOD-17708 | biostudies-arrayexpress
Project description:The clinical response to chemotherapy regimen of cisplatin and paclitaxel in lung adenocarcinoma is frequently limited in magnitude and duration due to drug resistance. Recently, epithelial-mesenchymal transition (EMT) was associated with drug resistance. However, the underlying mechanisms remain elusive. To discover mechanisms of resistance, we developed the epithelial-like and mesenchymal-like A549 cell lines (lung adenocarcinoma cell line), and have their lncRNA expressions profiled and compared. Results provide insight into the molecular mechanisms underlying chemotherapy-resistance.
2019-12-31 | GSE129439 | GEO
Project description:Time Course of TGF-beta treatment of A549 lung adenocarcinoma cell line on Affymetrix HG_U133_plus_2 arrays; triplicate experiments. The goal of the experiment is to profile temporal gene expression changes during TGF-beta-induced epithelial-mesenchymal transition (EMT). During EMT cancer cells loose their epithelial specifc proteins and gain mesenchymal proteins to acquire migratory and invasive phenotype essential for metastasis. Human A549 lung adenocarcinoma cell line was treated with 5 ng/mL TGF-beta for 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 h to induce EMT. The experiment was repeated 3 times. Samples were assayed using Affymetrix HG_U133_plus_2 arrays with 54675 probe-sets, using standard techniques. We provide the raw .CEL files and a supplementary Excel spreadsheet with log-transformed data and selected results from a statistical analysis.
2009-08-20 | GSE17708 | GEO
Project description:The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states is critical to complete the metastatic process. In contrast, induction of epithelial-mesenchymal transition (EMT) through the acquisition of drug persistence is a more stable event. Herein, we utilize Her2 transformed human mammary epithelial (HMLE) cells to compare a reversible model of EMT induced by TGF-beta to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor, lapatinib. Indeed, only a TGF-beta cells capable of returning to an epithelial phenotype resulted in long bone metastasis (BM). These four cell populations were anylzed by RNA sequencing.
2019-06-04 | GSE115255 | GEO