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The murine whey acidic protein promoter directs expression to human mammary tumors after retroviral transduction

Cancer Gene Therapy volume 9, pages 421–431 (2002)Cite this article

Abstract

The whey acidic protein (WAP) promoter is known to be active in pregnant and lactating mammary epithelial cells as well as mammary tumors of mice. Here we show that a proximal fragment of the murine WAP promoter, including most elements postulated as being responsible for mammary-specific regulation, confers mammary-specific expression upon a marker gene in transgenic mice even though the distal promoter region, known to be important for rat WAP promoter activity, is lacking. The relatively small size of this fragment allows its insertion into a murine leukemia virus–based retroviral vector in place of the viral promoter. Infection of a number of established human mammary and nonmammary cell lines with such a retroviral vector revealed that the WAP promoter was limited in its activity to mammary tumor cell lines. Expression in tumorigenic mammary cells was even more pronounced when these cells were introduced into the mammary fat pads of mice. This is the first demonstration that the WAP promoter is active in human mammary cells and mammary tumor cells in general, and suggests that the extended proximal WAP promoter may be useful for directing therapeutic gene expression to human mammary tumors.

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Acknowledgements

We thank David Winder and Robert Saller for helpful advice. This project was financed, in part, by a grant from the Bavarian Forschungsstiftung FORGEN 2 programme.

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  1. Matthias Renner & Brian Salmons

    Present address: for Matthias Renner and Brian Salmons Austranova, Vienna, A-1210, Austria

Authors and Affiliations

  1. Institute of Virology, University of Veterinary Sciences, Vienna, A-1210, Austria

    Feride Öztürk-Winder, Dieter Klein & Walter H Günzburg

  2. Austrian–Nordic Biotherapeutics, Vienna, A-1210, Austria

    Matthias Renner & Brian Salmons

  3. Institute of Animal Breeding and Genetics, University of Veterinary Sciences, Vienna, A-1210, Austria

    Mathias Müller

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  1. Feride Öztürk-Winder
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Correspondence to Walter H Günzburg.

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Öztürk-Winder, F., Renner, M., Klein, D. et al. The murine whey acidic protein promoter directs expression to human mammary tumors after retroviral transduction. Cancer Gene Ther 9, 421–431 (2002). https://doi.org/10.1038/sj.cgt.7700456

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