Expression profiling of MDA-MB-231 breast cancer cells treated with DOT1L inhibitors and siDOT1L
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Zhang L
PROVIDER: S-ECPF-GEOD-56630 | biostudies-other | 2014 Nov
REPOSITORIES: biostudies-other
Similar Datasets
Project description:MDA-MB-231 cell line with relatively high DOT1L levels was treated with two potent, selective inhibitors of the DOT1L histone methyl transferase. These compounds can inhibit cells migration and invasion and induce differentiation. Here we provide expression profiling data of cells treated with two DOT1L inhibitors [1] [2], DOT1L siRNA (siDOT1L) or control.
2015-02-18 | GSE56630 | GEO
Project description:MDA-MB-231 cell line with relatively high DOT1L levels was treated with two potent, selective inhibitors of the DOT1L histone methyl transferase. These compounds can inhibit cells migration and invasion and induce differentiation. Here we provide expression profiling data of cells treated with two DOT1L inhibitors [1] [2], DOT1L siRNA (siDOT1L) or control. MDA-MB-231 cells were treated with 1uM compound [1], 5uM compound [1], 2uM compound [2], 10 uM compound [2] (DOT1L inhibitors) or control (0.1% DMSO) for 14 days, or siDOT1L for 7 days. For each unique condition, 2 biological replicates were generated for expression profiling. Compound [1]: EPZ004777 (in Diagle et al., 2011) Compound [2]: Compound 55 (in Anglin et al., 2012)
2015-02-18 | E-GEOD-56630 | biostudies-arrayexpress
Project description:Microarray technology (Human OneArray microarray, phylanxbiotech.com) was used to compare gene expression profiles of non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells exposed to dioscin (DS), a steroidal saponin isolated from the roots of wild yam, (Dioscorea villosa). Initially the differential expression of genes (DEG) was identified which was followed by pathway enrichment analysis (PEA). Of the genes queried on OneArray, we identified 4641 DEG changed between MCF-7 and MDA-MB-231 cells (vehicle-treated) with cut-off log2 |fold change|≧1. Among these genes, 2439 genes were upregulated and 2002 were downregulated. DS exposure (2.30 μM, 72 h) to these cells identified 801 (MCF-7) and 96 (MDA-MB-231) DEG that showed significant difference when compared with the untreated cells (p<0.05). Within these gene sets, DS was able to upregulate 395 genes and downregulate 406 genes in MCF-7 and upregulate 36 and downregulate 60 genes in MDA-MB-231 cells. Further comparison of DEG between MCF-7 and MDA-MB-231 cells exposed to DS identified 3626 DEG of which 1700 were upregulated and 1926 were down-regulated. Regarding to PEA, 12 canonical pathways were significantly altered between these two cell lines. However, there was no alteration in any of these pathways in MCF-7 cells, while in MDA-MB-231 cells only MAPK pathway showed significant alteration. When PEA comparison was made on DS exposed cells, it was observed that only 2 pathways were significantly affected. Further, we identified the shared DEG, which were targeted by DS and overlapped in both MCF-7 and MDA-MB-231 cells, by intersection analysis (Venn diagram). We found that 7 DEG were overlapped of which six are reported in the database. This data highlight the diverse gene networks and pathways in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin.
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Project description:Parathyroid hormone-related protein (PTHrP) is overexpressed in many cancer types. This secretory protein can induce hypercalcaemia of malignancy by mimicking the action of calcium-regulating parathyroid hormone (PTH). PTHrP may also be involved in the regulation of migration, invasion, proliferation and apoptosis. It can either stimulate signal cascades, such as the cAMP pathway, or act on not yet defined targets in the nucleus. In this study, we analyzed the effect of PTHrP-specific siRNA on gene expression in MDA-MB-231 breast cancer cells. MDA-MB-231 cells were either transfected with the PTHrP-specific siRNA (siPTHrP) or a control siRNA (siLuc). Differences in gene expression pattern in siPTHrP- vs. siLuc-treated cells were measured by microarray analysis. More than 200 differentially expressed genes were found. Some of these genes have important functions in carcinogenesis. Experiment Overall Design: Three independent transfection experiments were performed. Cells were transfected with siPTHrP or siLuc by electroporation, grown for three days and harvested for isolation of total RNA. RNAs were subjected to microarray analysis. The RNAs of experiment 1 are designated as siLuc 1 and siPTHrP 1, those of experiment 2 as siLuc 2 and siPTHrP 2 etc.. To identify siPTHrP-responsive genes, the siPTHrP- and siLuc-RNAs of the same experiment were compared.
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Project description:Analogs of ManNAc, the committed precursor of sialic acid, decrease metastatic potential and trigger apoptosis in cancer cells. Adding Lev to ManNAc analogs increases their toxicity due to an ill-understood mechanism. Comparing gene expression profiles of cells treated with Ac4ManNLev and Ac4ManNAc will provide insight into the similarities and differences of these analogs. Specifically, MDA-MB-231 human breast cancer cells will be treated with Ac4ManNLev and Ac4ManNAc at doses that inhibit cell growth and induce the cell to undergo apoptosis later. RNA will be harvested in the early stage of cell arrest in order to identify genes altered by Ac4ManNLev and Ac4ManNAc. RNA preparations from three conditions, were sent to Microarray Core (E). One as control (Ethanol), and two experimental groups: high concentration Ac4ManNAc (100 uM) and high concentration Ac4ManNLev (100 uM). The aim is to gain insight into apoptosis and cell cycle arrest. Specifically, the Ac4ManNLev samples will be comprared to a less potent ManNAc analog. The RNA was amplified, labeled, and hybridized to the GLYCOv3 microarrays.
| S-ECPF-GEOD-28939 | biostudies-other
Project description:Bone sialoprotein (BSP) has become a target in breast cancer research as it is associated with tumor progression and metastasis. The mechanisms underlying the regulation of BSP expression have been largely elusive. Given that BSP is involved in the homing of cancer cells in bone metastatic niches, we addressed regulatory effects of proteolytic cleavage and extracellular matrix components on BSP expression and distribution in cell culture models. Therefore, MDA-MB-231 human breast cancer cells were kept in 2D and 3D spheroid cultures and exposed to basement membrane extract in the presence or absence of matrix metalloproteinase 9 or the non-polar protease, dispase. Confocal imaging of immunofluorescence samples stained with different antibodies against human BSP demonstrated a strong inducing effect of basement membrane extract on anti-BSP immunofluorescence. Similarly, protease incubation led to acute upregulation of anti-BSP immunofluorescence signals, which was blocked by cycloheximide, suggesting de novo formation of BSP. In summary, our data show that extracellular matrix components play an important function in regulating BSP expression and hint at mechanisms for the formation of bone-associated metastasis in breast cancer that might involve local control of BSP levels by extracellular matrix degradation and release of growth factors.
| S-EPMC8225072 | biostudies-literature
Project description:Elastin is a long-lived extracellular matrix protein responsible for the structural integrity and function of tissues. Breast cancer elastosis is a complex phenomenon resulting in both the deposition of elastotic masses and the local production of elastin fragments. In invasive human breast cancers, an increase in elastosis is correlated with severity of the disease and age of the patient. Elastin-derived peptides (EDPs) are a hallmark of aging and are matrikines - matrix fragments having the ability to regulate cell physiology. They are known to promote processes linked to tumor progression, but their effects on breast cancer cells remain unexplored. Our data show that EDPs enhance the invasiveness of MDA-MB-231 breast cancer cells through the engagement of matrix metalloproteases 14 and 2. We therefore suggest that elastosis and/or an aged stroma could promote breast cancer cell invasiveness.
| S-EPMC6120250 | biostudies-literature
Project description:In the past decades, altered Follistatin‑like 1 (FSTL1) expression has been documented in a variety of cancers, while its functional roles are poorly understood. Particularly in breast cancer, the expression of FSTL1 and its signaling pathway remain to be determined. In the present study, an elevated FSTL1 expression and a supressed cell proliferation were detected in a specific brain metastatic cell line MDA‑MB‑231‑BR (231‑BR), compared with its parental cell line MDA‑MB‑231. However, this protein was hardly detected in the other three breast cancer cell lines. Next, lentiviral vectors encoding FSTL1 or FSTL1 specific shRNAs were used to overexpress or knock down FSTL1 in MDA‑MB‑231 or 231‑BR, respectively (MDA‑MB‑231FSTL1 or 231‑BRsh FSTL1). Results showed that overexpression of FSTL1 inhibited MDA‑MB‑231 cell proliferation, while knockdown of FSTL1 in 231‑BR cells promotes cell proliferation, compared with their corresponding control groups. These results were further confirmed in nude mouse xenografts. The tumor volume in 231‑BR cell-bearing mice was significantly smaller than that of MDA‑MB‑231 group, and reduction of tumor volume was detected in MDA‑MB‑231FSTL1 cell-bearing mice compared with the control group. Previous studies revealed that TGF‑β-Smad2/3 signaling pathway was activated in 231‑BR and MDA‑MB‑231FSTL1 cells, which may contribute to the inhibited cell proliferation. In addition, Smad3 knockdown could restore the inhibition of cell proliferation induced by FSTL1 overexpression in MDA‑MB‑231FSTL1 cells, indicating that the anti‑proliferative effect of FSTL1 overexpression may be associated with Smad3 involved TGF‑β signaling pathway regulation. This study identified FSTL1 as an inhibitor of cell proliferation in MDA‑MB‑231 and 231‑BR cell lines, which may provide new insights into the development and management of breast cancer.
| S-EPMC5780039 | biostudies-literature
Project description:Breast cancer is an important worldwide public health concern. The incidence rate of breast cancer increases every year. The primary cause of death is metastasis, a process by which cancer cells spread from a primary site to secondary organs. MicroRNAs (miRs/miRNAs) are small non-coding RNAs that control gene expression at the post-transcriptional level. Dysregulation of certain miRNAs is involved in carcinogenesis, cancer cell proliferation and metastasis. Therefore, the present study assessed miRNAs associated with breast cancer metastasis using two breast cancer cell lines, the low-metastatic MCF-7 and the highly metastatic MDA-MB-231. miRNA array analysis of both cell lines indicated that 46 miRNAs were differentially expressed when compared between the two cell lines. A total of 16 miRNAs were upregulated in MDA-MB-231 compared with MCF-7 cells, which suggested that their expression levels may be associated with the highly invasive phenotype of MDA-MB-231 cells. Among these miRNAs, miR-222-3p was selected for further study and its expression was confirmed by reverse transcription-quantitative PCR (RT-qPCR). Under both non-adherent and adherent culture conditions, the expression levels of miR-222-3p in the MDA-MB-231 cell line were higher than those noted in the MCF-7 cell line under the same conditions. Suppression of endogenous miR-222-3p expression in MDA-MB-231 cells using a miR-222-3p inhibitor resulted in a 20-40% reduction in proliferation, and a ~30% reduction in migration, which suggested that the aggressive phenotype of MDA-MB-231 cells was partly regulated by miR-222-3p. Bioinformatic analysis of miR-222-3p using TargetScan 8.0, miRDB and PicTar identified 25 common mRNA targets, such as cyclin-dependent kinase inhibitor 1B, ADP-ribosylation factor 4, iroquois homeobox 5 and Bcl2 modifying factor. The results of the present study indicated that miR-222-3p was potentially associated with the proliferation and migratory ability of the MDA-MB-231 cell line.
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Project description:(1) Background: Amikacin is an aminoglycoside antibiotic used for treating gram-negative bacterial infections in cancer patients. In this study, our aims are to investigate the migratory inhibition effects of amikacin in human MDA-MB-231 cells. (2) Methods: We used a wound-healing assay, trans-well analysis, Western blotting, immunostaining and siRNA knockdown approaches to investigate how amikacin influenced MDA-MB-231 cell migration and invasion. (3) Results: Wound healing showed that the MDA-MB-231 cell migration rates decreased to 44.4% in the presence of amikacin. Trans-well analysis showed that amikacin treatment led to invasion inhibition. Western blotting demonstrated that amikacin induced thioredoxin-interacting protein (TXNIP) up-regulation. TXNIP was knocked down using siRNA in MDA-MB-231 cell. Using immunostaining analysis, we found that inhibition of TXNIP expression led to MDA-MB-231 pseudopodia extension; however, amikacin treatment attenuated the cell extension formation. (4) Conclusions: We observed inhibition of migration and invasion in MDA-MB-231 cells treated with amikacin. This suggests inhibition might be mediated by up-regulation of TXNIP.
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