Transcription profiling of by comparing human breast cancer cell line MDA-MB-468 cyclin E transfected cells with control-transfected cells vs a control
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Berglund P
PROVIDER: S-ECPF-MEXP-339 | biostudies-other | 2005 Nov
REPOSITORIES: biostudies-other
Similar Datasets
Project description:We studied the effect of cyclin E overexpression in the breast cancer cell line MDA-MB-468, by comparing cyclin E transfected cells with control-transfected cells. The cyclin E/control hybridization was performed twice and cDNA from control transfected cells was used as a reference.
2005-05-31 | E-MEXP-339 | biostudies-arrayexpress
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).
| S-ECPF-GEOD-18571 | biostudies-other
Project description:Transcriptional profiling of breast cancer cells comparing LNA-control transfected cells with cells transfected with LNA-antimiR-21.We searched for miR-21 targets by systematic screening of mRNA profiling of LNA-antimiR-21 transfected MCF-7 cells and MDA-MB-231 cells. Two-condition experiment, LNA-antimiR-21 Transfected vs. LNA-control Transfected MCF-7 cells. One replicate per array.
| S-ECPF-GEOD-20627 | biostudies-other
Project description:Transcriptional profiling of breast cancer cells comparing pre-control transfected cells with cells transfected with pre-miR-125b. We searched for miR-125b targets by systematic screening of mRNA profiling of pre-miR-125b transfected MCF-7 cells and MDA-MB-435 cells. Two-condition experiment, pre-miR-125b Transfected vs. pre-control Transfected MCF-7 cells. One replicate per array.
| S-ECPF-GEOD-22546 | biostudies-other
Project description:To determine the effect ALDH1A3 expression on global gene expression in MDA-MB-231 cells and MDA-MB-468 cells In MDA-MB-231 cells, ALDH1A3 was overexperssed (have low endogenous levels of ALDH1A3) and compared to MSCV empty vector control. In MDA-MB-468 cells that have high endogenous levels of ALDH1A3, ALDH1A3 expresion was reduced with ALDH1A3 shRNA1 and compared to scramble shRNA control.
| S-ECPF-GEOD-49322 | biostudies-other
Project description:The functional characteristics of membrane progesterone receptors (mPRs) have been investigated using recombinant mPR proteins over-expressed in MDA-MB-231 breast cancer cells. Although these cells do not express the full-length progesterone receptor (PR), it is not known whether they express N-terminally truncated PR isoforms which could possibly account for some progesterone receptor functions attributed to mPRs. In the present study, the presence of N-terminally truncated PR isoforms was investigated in untransfected and mPR-transfected MDA-MB-231 cells, and in MDA-MB-468 breast cancer cells. PCR products were detected in PR-positive T47D Yb breast cancer cells using two sets of C-terminus PR primers, but not in untransfected and mPR-transfected MDA-MB-231 cells, nor in MDA-MB-468 cells. Western blot analysis using a C-terminal PR antibody, 2C11F1, showed the same distribution pattern for PR in these cell lines. Another C-terminal PR antibody, C-19, detected immunoreactive bands in all the cell lines, but also recognized α-actinin, indicating that the antibody is not specific for PR. High affinity progesterone receptor binding was identified on plasma membranes of MDA-MB-468 cells which was significantly decreased after treatment with siRNAs for mPRα and mPRβ. Plasma membranes of MDA-MB-468 cells showed very low binding affinity for the PR agonist, R5020, ≤1% that of progesterone, which is characteristic of mPRs. Progesterone treatment caused G protein activation and decreased production of cAMP in MDA-MB-468 cells, which is also characteristic of mPRs. The results indicate that the progestin receptor functions in these cell lines are mediated through mPRs and do not involve any N-terminally truncated PR isoforms.
| S-EPMC3129471 | biostudies-literature
Project description:A number of studies have indicated that thyroid hormone receptor β1 (TRβ1) functions as a tumor suppressor. TRs mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). A novel rat TRβ isoform (rTRβΔ) was previously identified, in which a novel exon, N (108 bp), is located between exons 3 and 4 within the DBD; this exon represents the only difference between rTRβΔ and rTRβ1. In vitro, rTRβΔ exhibits a stronger tumor-suppressive capacity than rTRβ1, and further analysis revealed a high level of conservation between the rat and human DBD sequences. In the present study, an artificially modified human TRβ1 (m-hTRβ1) was constructed via the introduction of the 108-bp sequence into the corresponding position of the wild-type human TRβ1 (wt-hTRβ1) DBD. An electrophoretic mobility shift assay and transfection experiments confirmed that m-hTRβ1 is functional. Overexpression of m-hTRβ1 inhibits the proliferation of MDA-MB-468 cells in the presence of triiodothyronine by promoting apoptosis, which may be associated with the upregulation of Caspase-3 and Bak gene expression and the activation of the Caspase-3 protein. In addition, the pro-apoptotic effect of m-hTRβ1 was stronger, compared with wt-hTRβ1. These results indicated that m-hTRβ1 may act as a tumor suppressor in MDA-MB-468 cells. These data provided a novel insight into gene therapy for breast cancer.
| S-EPMC6019938 | biostudies-literature
Project description:Identification of MUC4-associated expression of genes by comparing MUC4 knockdown (MDA-MB-231-shMUC4) and control (MDA-MB-231-SCR).
2012-12-31 | GSE40157 | 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.
2009-11-20 | GSE18571 | GEO
Project description:Tumor proliferation, drug resistance and cell stemness are major difficulties that are encountered during breast cancer therapy and are often responsible for disease progression and cancer-related mortality. β-catenin is considered to be an invasion gene in breast cancer. However, how β-catenin regulates breast cancer cell proliferation and stemness remains unclear. In the present study, β-catenin knockdown by small interfering RNA in MDA-MB-468, a highly metastatic breast cancer cell line, inhibited the expression of β-catenin, Oct3/4 (stemness), survivin (anti-apoptosis) and BCRP (drug resistance). Knockdown of β-catenin enhanced the effects of fluorouracil (5-FU) chemotherapy on the proliferation of MDA-MB-468 cells. Thus, these preliminary results indicate that β-catenin knockdown enhanced 5-FU-induced proliferation inhibition in the breast cancer cell line MDA-MB-468, and indicate that combining 5-FU with gene silencing could be an advantageous option for enhancing the curative effect of chemotherapy in breast cancer and other malignancies.
| S-EPMC4179739 | biostudies-literature