CYCLIN D1 TRANSGENE IMPEDES LYMPHOCYTE MATURATION AND COLLABORATES IN LYMPHOMAGENESIS WITH THE MYC GENE
CYCLIN D1 TRANSGENE IMPEDES LYMPHOCYTE MATURATION AND COLLABORATES IN LYMPHOMAGENESIS WITH THE MYC GENE
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DOI：
10.1002/j.1460-2075.1994.tb06488.x
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发表时间：
1994-05-01
期刊：
影响因子：
11.4
通讯作者：
ADAMS, JM
中科院分区：
文献类型：
--
作者：
BODRUG, SE;WARNER, BJ;ADAMS, JM
细胞周期蛋白D1是某些蛋白激酶的调节亚基，被认为可以推进细胞周期的G（1）期。细胞周期蛋白D1表达失调与几种人类肿瘤有关，最一致的是中心细胞型B淋巴瘤，其中细胞周期蛋白D1基因通常已易位到免疫球蛋白位点。为了直接确定组成型细胞周期蛋白D1表达是否是淋巴瘤发生的，产生了具有与免疫球蛋白增强子连接的细胞周期蛋白D1基因的转基因小鼠。尽管大量的转基因表达，他们的淋巴细胞在细胞周期活动，大小和有丝分裂原反应是正常的，但年轻的转基因动物含有较少的成熟B-和T-细胞。虽然自发性肿瘤是罕见的，淋巴瘤的发生是更迅速的共同表达的细胞周期蛋白D1转基因和myc转基因的小鼠比单独表达任一转基因的小鼠。此外，myc转基因动物的自发性淋巴瘤往往异位表达内源性细胞周期蛋白D1基因。这些发现表明，这种G（1）细胞周期蛋白可以调节分化，并在肿瘤发生中与myc样基因合作。
Cyclin D1 is the regulatory subunit of certain protein kinases thought to advance the G(1) phase of the cell cycle. Deregulated cyclin D1 expression has been implicated in several human neoplasms, most consistently in centrocytic B lymphoma, where the cyclin D1 gene usually has been translocated to an immunoglobulin locus. To determine directly whether constitutive cyclin D1 expression is lymphomagenic, transgenic mice were generated having the cyclin D1 gene linked to an immunoglobulin enhancer. Despite abundant transgene expression, their lymphocytes were normal in cell cycle activity, size and mitogen responsiveness, but young transgenic animals contained fewer mature B- and T-cells. Although spontaneous tumours were infrequent, lymphomagenesis was much more rapid in mice that co-expressed the cyclin D1 transgene and a myc transgene than in mice expressing either transgene alone. Moreover, the spontaneous lymphomas of myc transgenic animals often ectopically expressed the endogenous cyclin D1 gene. These findings indicate that this G(1) cyclin can modulate differentiation and collaborate with myc-like genes in oncogenesis.