Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras
Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras
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DOI：
10.1038/sj.onc.1202880
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发表时间：
1999-09-02
期刊：
影响因子：
8
通讯作者：
Serrano, M
中科院分区：
文献类型：
--
作者：
Pantoja, C;Serrano, M
细胞周期抑制物p21在衰老过程中上调，在致癌的PAS诱导衰老样停滞时，我们使用来自p21缺失小鼠的原代成纤维细胞来评估p21在这些过程中的作用。我们发现原代p21(-/-)细胞进入衰老，其寿命与野生型细胞相似。在永生化后，大多数野生型和p21(-/-)培养物获得p53或p16(INK4a)的改变，进一步表明p21缺乏本身不足以使永生化。原代p21(-/-)细胞和野生型细胞一样，通过积聚p53和p16(INK4a)并通过降低它们的增殖率来响应致癌的PAS。与此相一致的是，与p53(-/-)细胞相比，p21(-/-)细胞对癌基因RAS的肿瘤转化是不耐受的。我们的结论是，在小鼠成纤维细胞中，p21既不是衰老所必需的，也不是通过致癌RAS来阻止肿瘤转化所必需的。
The cell-cycle inhibitor p21 is upregulated during senescence and upon induction of senescence-like arrest by oncogenic Pas, We have used primary fibroblasts derived from p21-null mice to evaluate the role of p21 in these processes. We find that primary p21(-/-) cells enter senescence and have a lifespan similar to wild-ta pe cells. Upon immortalization, most wild-type and p21(-/-) cultures acquire alterations in either p53 or p16(INK4a), further indicating that p21-deficiency is not sufficient by itself to allow immortalization. Primary p21(-/-) cells, like wild-type cells, respond to oncogenic Pas by accumulating p53 and p16(INK4a), and by decreasing their proliferation rate. In agreement with this, p21(-/-) cells are refractory to neoplasic transformation by oncogenic Ras when compared to p53(-/-) cells. We conclude that, in murine fibroblasts, p21 is not essential neither for senescence nor for preventing neoplasic transformation by oncogenic Ras.