Faculty Research 1990 - 1999

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

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Cell-Division: ge, ph, Cell-Transformation-Neoplastic, Cells-Cultured, Cyclic-AMP: ph, Cyclins: ge, ph, Female, Forskolin, FSH: ph, Gene-Dosage, Gene-Expression-Regulation, Gene-Targeting, Granulosa-Cells: cy, Human, Infertility-Female: ge, Male, Mice, Ovarian-Neoplasms: me, Ovary: cy, ph, RNA-Messenger: me, Spermatogenesis: ph, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Testicular-Neoplasms: me, Testis: cy, ph, Tumor-Cells-Cultured

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Nature 1996 Dec 5;384(6608):470-4


THE D-type cyclins (D1, D2 and D3) are critical governors of the cell-cycle clock apparatus during the G1 phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues. 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.