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Published in: Breast Cancer Research 2/2005

Open Access 01-04-2005 | Research article

Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in vitro and in vivo

Authors: Yi-hua Wang, Shuang Liu, Guo Zhang, Cui-qi Zhou, Hong-xia Zhu, Xiao-bo Zhou, Lan-ping Quan, Jin-feng Bai, Ning-zhi Xu

Published in: Breast Cancer Research | Issue 2/2005

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Abstract

Introduction

Breast cancer is the leading cause of cancer death in women worldwide. Elevated expression of c-Myc is a frequent genetic abnormality seen in this malignancy. For a better understanding of its role in maintaining the malignant phenotype, we used RNA interference (RNAi) directed against c-Myc in our study. RNAi provides a new, reliable method to investigate gene function and has the potential for gene therapy. The aim of the study was to examine the anti-tumor effects elicited by a decrease in the protein level of c-Myc by RNAi and its possible mechanism of effects in MCF-7 cells.

Method

A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting c-myc to reduce its expression in MCF-7 cells. Western blot analysis was used to measure the protein level of c-Myc. We assessed the effects of c-Myc silencing on tumor growth by a growth curve, by soft agar assay and by nude mice experiments in vivo. Standard fluorescence-activated cell sorter analysis and TdT-mediated dUTP nick end labelling assay were used to determine apoptosis of the cells.

Results

Our data showed that plasmids expressing siRNA against c-myc markedly and durably reduced its expression in MCF-7 cells by up to 80%, decreased the growth rate of MCF-7 cells, inhibited colony formation in soft agar and significantly reduced tumor growth in nude mice. We also found that depletion of c-Myc in this manner promoted apoptosis of MCF-7 cells upon serum withdrawal.

Conclusion

c-Myc has a pivotal function in the development of breast cancer. Our data show that decreasing the c-Myc protein level in MCF-7 cells by RNAi could significantly inhibit tumor growth both in vitro and in vivo, and imply the therapeutic potential of RNAi on the treatment of breast cancer by targeting overexpression oncogenes such as c-myc, and c-myc might be a potential therapeutic target for human breast cancer.
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Metadata
Title
Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in vitro and in vivo
Authors
Yi-hua Wang
Shuang Liu
Guo Zhang
Cui-qi Zhou
Hong-xia Zhu
Xiao-bo Zhou
Lan-ping Quan
Jin-feng Bai
Ning-zhi Xu
Publication date
01-04-2005
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2005
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr975

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