Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis

Nature volume 384, pages 470–474 (1996)Cite this article

Abstract

THE D-type cyclins (Dl, D2 and D3) are critical governors of the cell-cycle clock apparatus during the Gl phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues1,2. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2−/− ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Sherr, C. J. Cell 79, 551–555 (1994).

    CAS  Article  Google Scholar 

  2. Peters, G. J. Cell Sci. (suppl.) 18, 89–96 (1994).

    CAS  Article  Google Scholar 

  3. Sicinski, P. et al. Cell 82, 621–630 (1995).

    CAS  Article  Google Scholar 

  4. Fantl, V., Stamp, G., Andrews, A., Rosewell, I. & Dickson, C. Genes Dev. 9, 2364–2372 (1995).

    CAS  Article  Google Scholar 

  5. Hogan, B., Beddington, R., Constantini, F. & Lacy, E. Manipulating the Mouse Embryo: A Laboratory Manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1994).

    Google Scholar 

  6. Richards, J. S. Endocr. Rev. 15, 725–751 (1994).

    CAS  Article  Google Scholar 

  7. O'Brien, M. J., Wigglesworth, K. & Eppig, J. J. Methods Toxicol. 38, 128–141 (1993).

    Google Scholar 

  8. Johnson, L. D., Albertini, D. F., McGinnis, L. K. & Biggers, J. D. J. Reprod. Fertil. 104, 277–284 (1995).

    CAS  Article  Google Scholar 

  9. Roger, P. P., Reuse, S., Maenhaut, C. & Dumont, J. E. Vitam. Horm. 51, 59–191 (1995).

    CAS  Article  Google Scholar 

  10. Desjardins, C. & Ewing, L. L. Cell and Molecular Biology of the Testis (Oxford University Press, New York, 1993).

    Google Scholar 

  11. Nakayama, H. et al. Dev. Growth Differ. 38, 141–151 (1996).

    CAS  Article  Google Scholar 

  12. Buckley, M. F. et al. Oncogene 8, 2127–2133 (1993).

    CAS  PubMed  Google Scholar 

  13. Bartkova, J. et al. Int. J. Cancer 57, 353–361 (1994).

    CAS  Article  Google Scholar 

  14. Inaba, T. et al. Genomics 13, 565–574 (1992).

    CAS  Article  Google Scholar 

  15. Bosl, G. J. et al. J. Natl Cancer Inst. 81, 1874–1878 (1989).

    CAS  Article  Google Scholar 

  16. Rodriguez, E. et al. Cancer Res. 52, 2285–2291 (1992).

    CAS  PubMed  Google Scholar 

  17. Suijkerbuijk, R. F. et al. Cancer Genet. Cytogenet. 101, 85–93 (1993).

    Article  Google Scholar 

  18. Boland, N. I. & Gosden, R. G. J. Reprod. Fertil. 10, 369–374 (1994).

    Article  Google Scholar 

  19. Fitzpatrick, S. L. & Richards, J. S. Endrocrinology 129, 1452–1462 (1991).

    CAS  Article  Google Scholar 

  20. Pelham, H. R. B. Cell 30, 517–528 (1982).

    CAS  Article  Google Scholar 

  21. Ausubel, F. M. et al. Current Protocols in Molecular Biology 4.2.4–4.2.6 (Wiley, New York, 1995).

    Google Scholar 

  22. Geng, Y. & Weinberg, R. A. Proc. Natl Acad. Sci. USA 90, 10315–10319 (1993).

    ADS  CAS  Article  Google Scholar 

Download references

Author information

Affiliations

  1. Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02142, USA

    Piotr Sicinski, Joana Liu Donaher, Yan Geng, Mary Y. Park & Robert A. Weinberg

  2. Howard Hughes Medical Institute, Verna and Mars McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas, 77030, USA

    Susan B. Parker & Stephen J. Elledge

  3. Department of Cell Biology, Baylor College of Medicine, Houston, Texas, 77030, USA

    Rebecca L Robker & JoAnne S. Richards

  4. Department of Cell Biology, The Scripps Research Institute, La Jolla, California, 92037, USA

    Humphrey Gardner

  5. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Lynda K. McGinnis & John D. Biggers

  6. The Jackson Laboratory, Bar Harbor, Maine, 04609, USA

    John J. Eppig

  7. Department of Pathology, Tufts University Schools of Medicine and Veterinary Medicine, Boston, Massachusetts, 02111, USA

    Roderick T. Bronson

Authors
  1. Piotr Sicinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joana Liu Donaher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan B. Parker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Humphrey Gardner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mary Y. Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rebecca L Robker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. JoAnne S. Richards
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lynda K. McGinnis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. John D. Biggers
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. John J. Eppig
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Roderick T. Bronson
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Stephen J. Elledge
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Robert A. Weinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sicinski, P., Donaher, J., Geng, Y. et al. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis. Nature 384, 470–474 (1996). https://doi.org/10.1038/384470a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/384470a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing