Accumulation of p(16INK4a) in mouse fibroblasts as a function of replicative senescence and not of retinoblastoma gene status
Accumulation of p(16INK4a) in mouse fibroblasts as a function of replicative senescence and not of retinoblastoma gene status
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DOI：
10.1038/sj.onc.1201212
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发表时间：
1997-07-31
期刊：
影响因子：
8
通讯作者：
Peters, G
中科院分区：
文献类型：
--
作者：
Palmero, I;McConnell, B;Peters, G
小鼠和人成纤维细胞的病毒转化对细胞周期蛋白依赖性激酶（Cdk）复合物的组成有非常不同的影响。在猴病毒40大t抗原（SV40 T-Ag）转化的人类细胞和缺乏功能性视网膜母细胞瘤基因产物（pRb）的人类肿瘤细胞系中，由于所有可用的Cdk4都与cdk抑制剂p16（INK4a）相关，因此无法检测到细胞周期蛋白D1-Cdk4复合物。相比之下，sv40转化的小鼠细胞和来自rb1无合子小鼠胚胎的成纤维细胞含有正常水平的细胞周期蛋白D1-Cdk4复合物。为了研究这种物种差异，我们比较了小鼠p16（INK4a）的生化特性和表达与人类的对应物。当原代胚胎成纤维细胞在培养中接近其有限寿命时，p16 RNA和蛋白水平显著增加，但小鼠p16表达似乎不受pRb状态的影响。因此，转化或自发永生化的小鼠细胞不能达到prb阴性的人类细胞系所具有的非常高的p16水平。我们认为这些差异可能与小鼠和人类细胞在培养中不朽的不同频率有关。
Viral transformation of mouse and human fibroblasts has very different effects on the composition of cyclin-dependent kinase (Cdk) complexes. In human cells transformed by the large T-antigen of simian virus 40 (SV40 T-Ag) and human tumour cell lines that lack a functional retinoblastoma gene product (pRb) no cyclin D1-Cdk4 complexes can be detected because all the available Cdk4 is associated with the Cdk-inhibitor p16(INK4a). In contrast, SV40-transformed mouse cells and fibroblasts from Rb1-nullizygous mouse embryos contain normal levels of cyclin D1-Cdk4 complexes. To investigate this species difference, we have compared the biochemical properties and expression of mouse p16(INK4a) with that of its human counterpart. There is a marked increase in p16 RNA and protein levels as primary embryo fibroblasts approach their finite lifespan in culture, but mouse p16 expression does not appear to be influenced by the status of pRb. Transformed or spontaneously immortalized mouse cells therefore do not achieve the very high levels of p16 characteristic of pRb-negative human cell lines. We suggest that these differences may be related to the different frequencies with which mouse and human cells can be immortalized in culture.