Transient expression of cyclin D1 is sufficient to promote hepatocyte replication and liver growth in vivo.
Transient expression of cyclin D1 is sufficient to promote hepatocyte replication and liver growth in vivo.
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发表时间：
2001-12
期刊：
影响因子：
11.2
通讯作者：
C. Nelsen;David G. Rickheim;N. Timchenko;M. Stanley;J. Albrecht
中科院分区：
文献类型：
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作者：
C. Nelsen;David G. Rickheim;N. Timchenko;M. Stanley;J. Albrecht
在培养的细胞中，细胞周期蛋白D1通过G(1)期调节丝裂原依赖的进程，其在恶性细胞中的过度表达被认为有助于体内的自主增殖。然而，以前在细胞系中的研究并没有证明细胞周期蛋白D1足以触发细胞复制。在这项研究中，我们发现瞬时转导成年肝细胞可刺激活性的细胞周期蛋白D1/CDK4复合体的组装、强劲的肝细胞增殖和完整动物的肝脏生长。几天后，尽管高水平的细胞周期蛋白D1和细胞周期蛋白E持续存在，但肝细胞的增殖受到抑制，这表明诱导了内源性的抗增殖机制。我们的数据表明，这种抗增殖反应包括p21的显著上调，这反过来又抑制了Cyclin D1/CDK4和Cyclin E/CDK2复合体。本研究进一步证明了细胞周期蛋白D1在肝细胞增殖调控中起着关键作用。此外，该模型可能为研究活体细胞对细胞周期蛋白D1表达的正常反应提供一个独特的系统。
Cyclin D1 regulates mitogen-dependent progression through G(1) phase in cultured cells, and its overexpression in malignant cells is thought to contribute to autonomous proliferation in vivo. However, previous studies in cell lines have not demonstrated that cyclin D1 is sufficient to trigger cell replication. In this study, we found that transient transfection of adult hepatocytes with cyclin D1 stimulated assembly of active cyclin D1/cdk4 complexes, robust hepatocyte proliferation, and liver growth in the intact animal. After several days, hepatocyte proliferation was inhibited despite the persistence of high levels of cyclin D1 and cyclin E, suggesting that endogenous antiproliferative mechanisms were induced. Our data suggest that this antiproliferative response includes the marked up-regulation of p21, which in turn inhibits cyclin D1/cdk4 and cyclin E/cdk2 complexes. This study offers further evidence that cyclin D1 plays a pivotal role in the regulation of hepatocyte proliferation in the liver. Furthermore, this model may offer a unique system to study the normal cellular response to cyclin D1 expression in vivo.