Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA120271 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes) may also be used to simulate a biologic process of effects of a drug treatment. In this study, we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer. Results: Colony formation and sulforhodamine B (IC50 < 1nM) assays, and xenograft animals showed that MDA-MB-468 cells were sensitive to treatment with rapamycin. The comparison of in vitro and in vivo gene expression data identified a signature, termed rapamycin metagene index (RMI), of 31 genes upregulated by rapamycin treatment in vitro as well as in vivo (false discovery rate of 10%). In the Miller dataset, RMI was significantly associated with tumor size or lymph node status. High (>75) percentile) RMI was significantly associated with longer survival (P = 0.015). On multivariate analysis, RMI (P = 0.029), tumor size (P = 0.015) and lymph node status (P = 0.01) were prognostic. In van 't Veer study, RMI was not associated with the time to develop distant metastasis (P = 0.41). In Wang dataset, RMI predicted time to disease relapse (P = 0.09). Conclusions: Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment. Mol Cancer. 2009 Sep 24;8(1):75. Experiment Overall Design: Rapamycin treatment of MDA-MB-468 breast cancer cell line: Experiment Overall Design: MDA-MB-468 cell line was treated by DMSO (vehicle) and 100 nM rapamycin for 24 hours. We sought to identify differentially expressed genes. Experiment Overall Design: Rapamycin treatment of breast tumor xenografts: Experiment Overall Design: MDA-MB-468 cells were inoculated in the mammary fat pad of female nude mice. When resulting tumor volumes had reached 75-150 mm3, the mice were divided in four groups. Groups 1 and 2 received a single injection of DMSO (vehicle) or rapamycin (15 mg/kg) intraperitoneally and sacrificied 24 h later (1-day groups). Groups 3 and 4 received weekly injections of DMSO or rapamycin for 3 weeks and sacrificied 24 h after the last injection (22-day groups).
2009-12-02 | E-GEOD-18571 | biostudies-arrayexpress
Project description:G protein-coupled receptors (GPCRs) are the largest class of membrane-bound receptors and transmit critical signals from the extracellular to intracellular spaces. Transcriptomic data of resected breast tumors shows that low mRNA expression of the orphan GPCR GPR52 correlates with reduced overall survival in breast cancer patients, leading to the hypothesis that loss of GPR52 supports breast cancer progression. CRISPR-Cas9 was used to knockout GPR52 in human triple-negative breast cancer (TNBC) cell lines MDA-MB-468 and MDA-MB-231, and in the non-cancerous breast epithelial cell line, MCF10A. Loss of GPR52 was found to be associated with increased cell-cell interaction in 2D cultures, altered 3D morphology and increased propensity to organize and invade collectively in Matrigel. Furthermore, GPR52 loss was associated with features of EMT in MDA-MB-468 cells. To determine the in vivo impact of GPR52 loss, MDA-MB-468 cells were injected into zebrafish and loss of GPR52 was associated with a greater total cancer area compared to control cells. RNA-sequencing analyses of GPR52-null MDA-MB-468 cells and resected breast tumors reveal an increased cAMP signaling signature. Consistently, we found that treatment of wild-type cells with forskolin, which stimulates production of cAMP, induces some phenotypic changes associated with GPR52 loss, and inhibition of cAMP production rescued some of the GPR52 KO phenotypes. Overall, our results reveal GPR52 loss as a potential mechanism by which breast cancer progression may occur and support the investigation of GPR52 agonism as a therapeutic option in breast cancer.
2025-07-26 | GSE273237 | GEO
Project description:We analysed aquired chemotherapeutic resistance of two different triple negative breast cancer cell lines BT-549 (Doxorubicin resistance) and MDA-MB-468 (5-Fluorouracil) by comparing the proteome of the parental cell line with the resistant cell line.
2018-02-23 | PXD008522 | Pride
Project description:The impact of three different chemodrugs (Adriamycin, Taxotere, Cytoxan) on the breast cancer cell line (MDA-MB-468) was analyzed compared to the parental cell by RNA-sequencing.
2023-04-22 | GSE230273 | GEO
Project description:Over-expression of miR-522 mimic or control miR mimic in MDA-MB-468 breast cancer cell line
2014-06-30 | E-MTAB-2110 | biostudies-arrayexpress
Project description:This study was designed to investigate the Metformin mode of action in different subtypes of breast cancer using cell and molecular, and systems biology techniques. To that end, several concentrations of Metformin have been used. Besides, five different breast cancer cell lines representing the five breast cancer phenotypes have been employed in this study. These cell lines were BT-474, MCF-7, MDA-MB-231, MDA-MB-468, and SkBr3 as representative for (Luminal B, Luminal A, Claudin-low, Basal-like, and HER2) subtypes respectively. Interestingly, Metformin treatment significantly reduced cancer cell viability and proliferation while inducing cell apoptosis and enhanced cell necrosis of the Basal-like (MDA-MB-468), although, the less sensitive subtype is HER2 (SkBr3).
2019-03-07 | E-MTAB-7737 | biostudies-arrayexpress
Project description:The goal of this work was to identify all estrogen receptor beta target genes using RNA sequencing in MDA-MB-468 triple negative breast cancer cells engineered with inducible expression of full length estrogen receptor beta. MDA-MB-468 breast cancer cells with inducible ERb expression (MDA-468-ERb cells) were treated in triplicate with vehicle (control, no ERb) or doxycycline (plus ERb) for 48 hr prior to treatment with 0.1% DMSO vehicle or 10 nM 17b-estradiol for 4 hr.
2015-08-12 | E-GEOD-71960 | biostudies-arrayexpress
Project description:Gene expression profiling by microarray analysis of tumors formed from inoculation of the established human breast cancer cell line MDA-MB-468 in two groups of mice: lean control and DIO mice.
2019-01-16 | GSE114604 | GEO
Project description:To investigate FOXC1 chromatin binding, and the effect of FOXC1 CRISPR knockout in triple negative breast cancer cell lines MDA-MB-231, MDA-MB-468, Hs578t, and Bt-549.
2024-06-14 | GSE213839 | GEO
Project description:To investigate FOXC1 chromatin binding, and the effect of FOXC1 CRISPR knockout in triple negative breast cancer cell lines MDA-MB-231, MDA-MB-468, Hs578t, and Bt-549.
2024-06-14 | GSE213840 | GEO