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Transforming growth factor alpha- and c-myc-induced mammary carcinogenesis in transgenic mice

Oncogene volume 19, pages 1092–1096 (2000)Cite this article

Abstract

The growth factor transforming growth factor alpha (TGFα) and the nuclear transcription factor c-myc often are overexpressed by human breast cancer cells. To produce models of breast disease with these etiologies, mice were generated that carried TGF-α- or c-myc-encoding transgenes. Transgene targeting employed the whey acidic protein (WAP) gene promoter, which is expressed in pregnant and lactating mammary epithelial cells. Non-virgin WAP-TGFα transgenic mice displayed accelerated mammary development during pregnancy, delayed post-parturient mammary involution, a progressive increase in the number of hyperplastic alveolar nodules (HANs), and development of mammary carcinoma with a mean latency of 9 months. Non-virgin WAP-c-myc transgenic mice displayed accelerated mammary gland development during pregnancy and development of mammary carcinomas with a latency of 8 months. Bitransgenic mice carrying both WAP-TGFα and WAP-c-myc displayed a dramatic acceleration of tumor development. These models identify the overexpression of TGFα or c-myc as etiological factors in the development of mammary neoplasia and demonstrate the increased severity of disease when both molecular alterations are present in the same cell.

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Acknowledgements

We acknowledge Dr David Lee and members of his laboratory, including Noreen Luetteke, Joyce Schroeder, and Ting Hui Qui, who participated in all phases of the studies summarized above. Research in this area in our laboratory was supported by NIH grants R01-CA64843 to EPS and K01-RR00145 to TR Hellekant.

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  1. Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive West, Madison, 53706, Wisconsin, WI, USA

    Teresa A Rose-Hellekant & Eric P Sandgren

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  1. Teresa A Rose-Hellekant
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  2. Eric P Sandgren
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Rose-Hellekant, T., Sandgren, E. Transforming growth factor alpha- and c-myc-induced mammary carcinogenesis in transgenic mice. Oncogene 19, 1092–1096 (2000). https://doi.org/10.1038/sj.onc.1203350

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