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Oncogenic role of DDX3 in breast cancer biogenesis

Oncogene volume 27, pages 3912–3922 (2008)Cite this article

Abstract

Benzo[a]pyrene diol epoxide (BPDE), the active metabolite of benzo[a]pyrene present in tobacco smoke, is a major cancer-causing compound. To evaluate the effects of BPDE on human breast epithelial cells, we exposed an immortalized human breast cell line, MCF 10A, to BPDE and characterized the gene expression pattern. Of the differential genes expressed, we found consistent activation of DDX3, a member of the DEAD box RNA helicase family. Overexpression of DDX3 in MCF 10A cells induced an epithelial-mesenchymal-like transformation, exhibited increased motility and invasive properties, and formed colonies in soft-agar assays. Besides the altered phenotype, MCF 10A-DDX3 cells repressed E-cadherin expression as demonstrated by both immunoblots and by E-cadherin promoter-reporter assays. In addition, an in vivo association of DDX3 and the E-cadherin promoter was demonstrated by chromatin immunoprecipitation assays. Collectively, these results demonstrate that the activation of DDX3 by BPDE, can promote growth, proliferation and neoplastic transformation of breast epithelial cells.

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Abbreviations

BPDE:

benzo[a]pyrene diol epoxide

ChIP:

chromatin immunoprecipitation

qRT–PCR:

quantitative real-time PCR

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Acknowledgements

This work was supported by a grant from the Fight Attendant Medical Research Institute (FAMRI) to Venu Raman. p21 promoter-reporter constructs were kindly provided by Dr Wafik El-Deiry (University of Pennsylvania).

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Authors and Affiliations

  1. Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    M Botlagunta, F Vesuna, Y Mironchik, A Lisok, P Winnard Jr, S Mukadam & V Raman

  2. Department of Biology, University of Maryland, Baltimore, MD, USA

    A Raman & P Farabaugh

  3. Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands

    P Van Diest

  4. Department of Life Science, Tzu Chi University, Hualien, Taiwan

    J H Chen

  5. Arvind Patel-Institute of Virology, Glasgow-G11, UK

    A H Patel

  6. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    V Raman

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  1. M Botlagunta
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Correspondence to V Raman.

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Botlagunta, M., Vesuna, F., Mironchik, Y. et al. Oncogenic role of DDX3 in breast cancer biogenesis. Oncogene 27, 3912–3922 (2008). https://doi.org/10.1038/onc.2008.33

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