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Parity-induced mammary epithelial cells facilitate tumorigenesis in MMTV-neu transgenic mice

Oncogene volume 23, pages 6980–6985 (2004)Cite this article

Abstract

Using a Cre-lox-based genetic labeling technique, we have recently discovered a parity-induced mammary epithelial subtype that is abundant in nonlactating and nonpregnant, parous females. These mammary epithelial cells serve as alveolar progenitors in subsequent pregnancies, and transplantation studies revealed that they possess features of multipotent progenitors such as self-renewal and the capability to contribute to ductal and alveolar morphogenesis. Here, we report that these cells are the cellular targets for transformation in MMTV-neu transgenic mice that exhibit accelerated mammary tumorigenesis in multiparous animals. The selective ablation of this epithelial subtype reduces the onset of tumorigenesis in multiparous MMTV-neu transgenics. There is, however, experimental evidence to suggest that parity-induced mammary epithelial cells may not be the only cellular targets in other MMTV-promoter-based transgenic strains. In particular, the heterogeneous MMTV-wnt1 lesions predominantly express the ductal differentiation marker Nkcc1 that is absent in MMTV-neu-derived tumors. Our observations support the idea that tumors originate from distinctly different epithelial subtypes in selected MMTV-promoter-driven cancer models and that diverse oncogenes might exert discrete effects on particular mammary epithelial subtypes.

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Acknowledgements

This work was supported, in part, by the Susan G Komen Breast Cancer Foundation (BCTR0402956) and a Public Health Service grant CA93797 from the National Cancer Institute. Support provided to KUW by the Nebraska Cancer and Smoking Disease Research Program (NE DHHS LB506) was imperative to finance in part the maintenance and analysis of the animal models. The UNMC Histology Core Facility is supported by the NCI Cancer Center Grant CA036727. We are grateful to Dr Robert D Cardiff (UC Davis) for his insight into the comparative analysis of histopathological features of mammary neoplasia and for providing histological slides from MMTV-wnt1 tumors. We also thank Jim Turner (National Institutes of Health, Bethesda) for contributing the Nkcc1 antibody to this study.

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Author notes

  1. MaLinda D Henry and Aleata A Triplett: These authors contributed equally to this work

Authors and Affiliations

  1. Eppley Institute for Research in Cancer and Allied Diseases and the Department of Pathology and Microbiology, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, 68198-6805, NE, USA

    MaLinda D Henry, Aleata A Triplett, Keon Bong Oh & Kay-Uwe Wagner

  2. Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg. 10, Room 5B56, 9000 Rockville Pike, Bethesda, 20892-1750, MD, USA

    Gilbert H Smith

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  1. MaLinda D Henry
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  2. Aleata A Triplett
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Correspondence to Kay-Uwe Wagner.

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Henry, M., Triplett, A., Oh, K. et al. Parity-induced mammary epithelial cells facilitate tumorigenesis in MMTV-neu transgenic mice. Oncogene 23, 6980–6985 (2004). https://doi.org/10.1038/sj.onc.1207827

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