Cyclin DZ is an FSH responsive gene involved in gonadal cell proliferation and oncogenesis
Cyclin DZ is an FSH responsive gene involved in gonadal cell proliferation and oncogenesis
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DOI：
10.1038/384470a0
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发表时间：
1996-12-05
期刊：
影响因子：
64.8
通讯作者：
Weinberg, RA
中科院分区：
文献类型：
--
作者：
Sicinski, P;Donaher, JL;Weinberg, RA
D型细胞周期蛋白（D1， D2和D3）是哺乳动物细胞周期G1期细胞周期时钟装置的关键调控因子。这三种d型细胞周期蛋白在增殖组织中以重叠、明显冗余的方式表达（1,2）。为了研究为什么哺乳动物细胞需要三种不同的d型细胞周期蛋白，我们在胚胎干细胞中使用基因靶向技术产生了携带破坏周期蛋白D2基因的小鼠。细胞周期蛋白d2缺陷的女性由于卵巢颗粒细胞在促卵泡激素（FSH）的作用下不能正常增殖而不育，而突变的男性则表现为睾丸发育不良。在卵巢颗粒细胞中，FSH通过cycllc-AMP依赖途径特异性诱导细胞周期蛋白D2，这表明各种d型细胞周期蛋白的表达受到不同的细胞内信号通路的控制。在周期蛋白D2（-/-）卵巢和睾丸中观察到的发育不全促使我们研究源自相应组织的人类癌症。我们发现一些人类卵巢和睾丸肿瘤含有高水平的细胞周期蛋白D2信使RNA。
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(1,2). 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 cycllc-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.