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Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice

Nature volume 369, pages 669–671 (1994)Cite this article

Abstract

PHYSICAL associations between cyclins, viral oncogenes and tumour suppressor genes imply a central role for cyclins in growth control1, 2. Cyclin D1 was identified as a candidate oncogene (PRAD1) in tumour-specific DNA rearrangements3, 4. and is suspected to be a contributor to several types of neoplasms including breast cancer5, 6. Cyclin D1 also rescues G1 cyclin-defective Saccharomyces cerevisiae7, and is a growth-regulated gene8. Despite evidence suggesting that cyclin D1 is an oncogene, its ability to transform cells directly in culture remains controversial9–16. To evaluate its potential to deregulate growth in vivo in a physiologically relevant tissue we overexpressed cyclin Dl in mammary cells in transgenic mice. We report here that overexpression of cyclin Dl resulted in abnormal mammary cell proliferation including the development of mammary adenocarcinomas. We conclude that overexpression of cyclin Dl deregulates cell proliferation and can induce tumorigenic changes in mammary tissues, suggesting that cyclin Dl indeed plays an important oncogenic role in breast cancer.

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References

  1. Whyte, P. et al. Nature 334, 124–129 (1988).

    Article  ADS  CAS  Google Scholar 

  2. Faha, B., Ewen, M. E., Tsai, L. H., Livingston, D. M. & Harlow, E. Science 255, 87–90 (1992).

    Article  ADS  CAS  Google Scholar 

  3. Rosenberg, C. L. et al. Proc. natn. Acad. Sci. U.S.A. 88, 9638–9642 (1991).

    Article  ADS  CAS  Google Scholar 

  4. Motokura, T. et al. Nature 350, 512–515 (1991).

    Article  ADS  CAS  Google Scholar 

  5. Lammie, G. A. et al. Oncogene 6, 439–444 (1991).

    CAS  PubMed  Google Scholar 

  6. Lammie, G. A. & Peters, G. Cancer Cells 3, 413–420 (1991).

    CAS  PubMed  Google Scholar 

  7. Xiong, Y., Connolly, T., Futcher, B. & Beach, D. Cell 65, 691–699 (1991).

    Article  CAS  Google Scholar 

  8. Matsushime, H., Roussel, M. F., Ashmun, R. A. & Sherr, C. J. Cell 65, 701–713 (1991).

    Article  CAS  Google Scholar 

  9. Hinds, P. W. et al. Cell 70, 993–1006 (1992).

    Article  CAS  Google Scholar 

  10. Baldin, V., Lukas, J., Marcote, M. J., Pagano, M. & Draetta, G. Genes Dev. 7, 812–821 (1993).

    Article  CAS  Google Scholar 

  11. Sherr, C. J. Cell 73, 1059–1065 (1993).

    Article  CAS  Google Scholar 

  12. Quelle, D. E. et al. Genes Dev. 7, 1559–1571 (1993).

    Article  CAS  Google Scholar 

  13. Rosenwald, I. B., Lazaris-Karatzas, A., Sonenberg, N. & Schmidt, E. V. Molec. cell. Biol. 13, 7358–7363 (1993).

    Article  CAS  Google Scholar 

  14. Jiang, W. et al. Oncogene 8, 3447–3464 (1993).

    CAS  PubMed  Google Scholar 

  15. Lovec, H., Sewing, A., Lucibello, F. C., Muiler, R. & Moroy, T. Oncogene 9, 323–326 (1994).

    CAS  PubMed  Google Scholar 

  16. Hinds, P. W., Dowdy, S. F., Eaton, E. N., Arnold, A. & Weinberg, R. A. Proc. natn. Acad. Sci. U.S.A. 91, 709–713 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Taketo, M. et al. Proc. natn. Acad. Sci. U.S.A. 88, 2065–2069 (1991).

    Article  ADS  CAS  Google Scholar 

  18. Casey, G., Smith, R., McGillivray, D., Peters, G. & Dickson, C. Molec. cell. Biol. 6, 502–510 (1986).

    Article  CAS  Google Scholar 

  19. Pathak, V. K., Strange, R., Young, L. J., Morris, D. W. & Cardiff, R. D. J. natn. Cancer Inst. 78, 327–331 (1987).

    CAS  Google Scholar 

  20. Yoshida, T. et al. Proc. natn. Acad. Sci. U.S.A. 84, 7305–7309 (1987).

    Article  ADS  CAS  Google Scholar 

  21. Peters, G., Brookes, S., Smith, R., Placzek, M. & Dickson, C. Proc. natn. Acad. Sci. U.S.A. 86, 5678–5682 (1989).

    Article  ADS  CAS  Google Scholar 

  22. Morris, D. W., Barry, P. A., Bradshaw, H. D. & Cardiff, R. D. J. Virol 64, 1794–1802 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Schuuring, E., Verhoeven, E., Mooi, W. J. & Michalides, R. J. Oncogene 7, 355–361 (1992).

    CAS  PubMed  Google Scholar 

  24. Borg, A. et al. Br. J. Cancer 63, 136–142 (1991).

    Article  CAS  Google Scholar 

  25. Rosen, P. P. Cancer 71, 3798–3807 (1993).

    Article  CAS  Google Scholar 

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Author notes

  1. Emmett V. Schmidt: To whom correspondence should be addressed

Authors and Affiliations

  1. Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA

    Timothy C. Wang

  2. Department of Pathology, School of Medicine, University of California at Davis, Davis, California, 95616, USA

    Robert D. Cardiff

  3. Laboratory of Endocrine Oncology, Department of Medicine and MGH Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA

    Lawrence Zukerberg & Andrew Arnold

  4. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA

    Lawrence Zukerberg

  5. MGH Cancer Center, Massachusetts General Hospital, Building 149, 13th street, Charlestown, Massachusetts, 02129, USA

    Emma Lees

  6. MGH Cancer Center and the Children's Service, Massachusetts General Hospital, Building 149, 13th street, Charlestown, Massachusetts, 02129, USA

    Emmett V. Schmidt

Authors
  1. Timothy C. Wang
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  2. Robert D. Cardiff
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  3. Lawrence Zukerberg
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  4. Emma Lees
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  5. Andrew Arnold
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  6. Emmett V. Schmidt
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Wang, T., Cardiff, R., Zukerberg, L. et al. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 369, 669–671 (1994). https://doi.org/10.1038/369669a0

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