Similar Datasets
Project description: Not available
| S-ECPF-GEOD-18571 | biostudies-other
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.
2009-11-20 | GSE18571 | GEO
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: Not available
| S-ECPF-GEOD-49322 | biostudies-other
Project description: Not available
| S-ECPF-MTAB-2119 | biostudies-other
Project description:We report the altered metabolite changes by processing CT mRNA in the TNBC cell line, MDA-MB-468. It was confirmed that the treatment of CT mRNA disrupted the synthesis of dTTP during nucleic acid metabolism, increasing the signal related to DNA damage in the cell, and that the energy metabolism and NADPH metabolism in the cell were changed for its recovery. The main energy sources, glucose metabolism and glutamine metabolism, are closely linked to the mitochondrial TCA cycle products. In the CT mRNA treatment group, intracellular nucleic acid depletion was observed to increase glutamine metabolism as a source of N source, and the pathway of aspartate utilization was observed. It was confirmed that it was expanded. As a result, a significant increase in the cysteine influx was observed according to the occurrence of ROS, and an effort to regulate the intracellular NADPH balance was observed through the change of metabolites over time. Finally, it was observed that the oncogenic pathway was significantly reduced in the CT mRNA-treated group compared with all untreated groups or controls with other substrate specificities. This study characterizes changes in intracellular metabolites caused by specific dTTP biosynthesis disturbances.
2022-05-06 | GSE202180 | GEO
Project description: Not available
| S-EPMC6019938 | biostudies-literature
Project description:The aim was to investigate the functional role of PLA2G7 in breast cancer using PLA2G7 silencing in cultured breast cancer cells. For stable knockdown of PLA2G7, shRNAs were transduced to MDA-MB-468 cells before genome-wide gene expression analysis. Gene expression profiles of the PLA2G7 silenced samples were compared with the scrambled control treated samples and two replicate samples were studied for each treatment.
2017-06-02 | E-MTAB-5398 | biostudies-arrayexpress
Project description:The aim was to investigate the functional role of PLA2G7 in breast cancer using transient PLA2G7 silencing in cultured breast cancer cells. For transient knockdown of PLA2G7, siRNA (SI00072177; siPLA2G7, Qiagen, Valencia, CA) was transfected to MDA-MB-468 cells and incubated 48 hours before genome-wide gene expression analysis. Gene expression profiles of the PLA2G7 silenced samples were compared with the scrambled control treated samples and two replicate samples were studied for each treatment.
2017-06-02 | E-MTAB-5397 | biostudies-arrayexpress
Project description:In this experiment, we generated isogenic carboplatin-resistant MDA-MB-468 cells displaying a 5x increase in IC50 in respect to the parental cell line. We set out to compare the transcriptome of these cell lines, together with MDA-MB-468 cells overexpressing a constitutively active form of beta-catenin to understand underlying transcriptional changes supporting stable carboplatin-tolerance.
2021-07-09 | E-MTAB-10337 | biostudies-arrayexpress