Dataset Information

?-catenin knockdown enhances the effects of fluorouracil in the breast cancer cell line MDA-MB-468.

ABSTRACT: 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. ?-catenin is considered to be an invasion gene in breast cancer. However, how ?-catenin regulates breast cancer cell proliferation and stemness remains unclear. In the present study, ?-catenin knockdown by small interfering RNA in MDA-MB-468, a highly metastatic breast cancer cell line, inhibited the expression of ?-catenin, Oct3/4 (stemness), survivin (anti-apoptosis) and BCRP (drug resistance). Knockdown of ?-catenin enhanced the effects of fluorouracil (5-FU) chemotherapy on the proliferation of MDA-MB-468 cells. Thus, these preliminary results indicate that ?-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.

SUBMITTER: Lv X

PROVIDER: S-EPMC4179739 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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β-catenin knockdown enhances the effects of fluorouracil in the breast cancer cell line MDA-MB-468.

Lv Xinquan X Pang Xia X Jin Xiangdong X Song Yimin Y Li Huixiang H

Biomedical reports 20140826 6

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 c ...[more]

PMID: 25279168

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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

?-catenin knockdown enhances the effects of fluorouracil in the breast cancer cell line MDA-MB-468.

Publications

<i>β-catenin</i> knockdown enhances the effects of fluorouracil in the breast cancer cell line MDA-MB-468.

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