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Transforming growth factors-β are not good biomarkers of chemopreventive efficacy in a preclinical breast cancer model system

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Abstract

Using a carcinogen-initiated rat model of mammary tumorigenesis, we tested the hypothesis that transforming growth factor (TGF)-βs are useful biomarkers of chemopreventive efficacy in the breast. The chemopreventive agents tested were tamoxifen and the retinoids 9-cis-retinoic acid (9cRA) and N-(4-hydroxyphenyl)retinamide (4-HPR), because both antiestrogens and retinoids have previously been shown to upregulate TGF-βs in vitro. Despite demonstrable chemopreventive efficacy in this model, none of these agents, alone or in combination, had any significant impact on the expression of TGF-βs in the mammary ductal epithelium or periductal stroma as determined by immunohistochemistry. These data suggest that TGF-βs are not likely to be useful biomarkers of chemopreventive efficacy in a clinical setting.

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Acknowledgements

We thank Drs Calle Heldin and Kohei Miyazono for the generous gift of Ab39, and Dr Clint Grubbs for the rat tissues treated with high levels of tamoxifen for short durations. We are grateful to Dr Donald Gardner for veterinary pathology expertise, to Dr Michael Sporn for many inspiring discussions on the concept and practice of chemoprevention, and to Dr Anita Roberts for continued support and guidance. This study was funded in part by an American Society of Clinical Oncology Young Investigator Award to Dr Zujewski.

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Authors and Affiliations

  1. Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

    Kathleen C Flanders & Lalage M Wakefield

  2. Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

    JoAnne Zujewski & Anika Vaughn-Cooke

  3. Veterinary Resources Program, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA

    Michael A Eckhaus

  4. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

    Ronald A Lubet

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  1. JoAnne Zujewski
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  2. Anika Vaughn-Cooke
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  3. Kathleen C Flanders
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  4. Michael A Eckhaus
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  5. Ronald A Lubet
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  6. Lalage M Wakefield
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Zujewski, J., Vaughn-Cooke, A., Flanders, K.C. et al. Transforming growth factors-β are not good biomarkers of chemopreventive efficacy in a preclinical breast cancer model system. Breast Cancer Res 3, 66 (2000). https://doi.org/10.1186/bcr273

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