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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.

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Authors and 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

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  1. Piotr Sicinski
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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

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