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Regulatory region of metastasis-inducing DNA is the binding site for T cell factor-4

Oncogene volume 20, pages 1793–1797 (2001)Cite this article

Abstract

Small 1000 bp fragments of DNA derived from human malignant breast cancer cells have been isolated which, when transfected into a benign rat mammary cell line induce the production of osteopontin and thereby endow those cells with the capability to metastasize in syngeneic rats. Using transient transfections of an osteopontin promoter-reporter construct, we have now identified the active moiety in the metastasis-inducing DNA as the binding site for the T cell factor (Tcf) family of transcription factors and located Tcf-4, β-catenin and E-cadherin in the relevant DNA complex in vitro. The regulatory effects of the metastasis-inducing DNAs are therefore exerted, at least in part, by a CAAAG sequence which can sequester Tcf-4, thereby promoting transcription of the direct effector for metastasis in this system, osteopontin.

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Acknowledgements

We thank Dr A Ridall, University of Texas for the original 6 kbp OPN promoter, Professor H Clevers, University of Utrecht for the cDNAs and antibodies to Tcf-1 and Tcf-4 and Drs N Sergeant and M Delehedde, University of Liverpool for advice on Western blotting. This work was supported by the Cancer and Polio Research Fund Ltd., UK.

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  1. Cancer and Polio Research Fund Laboratories, Molecular Medicine Group, School of Biological Sciences, University of Liverpool, Liverpool, L69 3BX, UK

    Mohamed K El-Tanani, Roger Barraclough, Mark C Wilkinson & Philip S Rudland

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  1. Mohamed K El-Tanani
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  2. Roger Barraclough
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  3. Mark C Wilkinson
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  4. Philip S Rudland
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El-Tanani, M., Barraclough, R., Wilkinson, M. et al. Regulatory region of metastasis-inducing DNA is the binding site for T cell factor-4. Oncogene 20, 1793–1797 (2001). https://doi.org/10.1038/sj.onc.1204358

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