Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide gene expression analysis of MDA-MB-468 human breast cancer cells treated with PLA2G7 siRNA

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Paula Vainio

PROVIDER: E-MTAB-5397 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

PLA2G7 associates with hormone receptor negativity in clinical breast cancer samples and regulates epithelial-mesenchymal transition in cultured breast cancer cells.

Lehtinen Laura L Vainio Paula P Wikman Harriet H Huhtala Heini H Mueller Volkmar V Kallioniemi Anne A Pantel Klaus K Kronqvist Pauliina P Kallioniemi Olli O Carpèn Olli O Iljin Kristiina K

The journal of pathology. Clinical research 20170404 2

Breast cancer is the leading cause of cancer-related deaths in women due to distinct cancer subtypes associated with early recurrence and aggressive metastatic progression. High lipoprotein-associated phospholipase A2 (PLA2G7) expression has previously been associated with aggressive disease and metastasis in prostate cancer. Here, we explore the expression pattern and functional role of PLA2G7 in breast cancer. First, a bioinformatic analysis of genome-wide gene expression data fr ...[more]

PMID: 28451461

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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).

Dataset Information

Genome-wide gene expression analysis of MDA-MB-468 human breast cancer cells treated with PLA2G7 siRNA

Publications

<i>PLA2G7</i> associates with hormone receptor negativity in clinical breast cancer samples and regulates epithelial-mesenchymal transition in cultured breast cancer cells.

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