CELLS EN-ROUTE TO APOPTOSIS ARE CHARACTERIZED BY THE UP-REGULATION OF C-FOS, C-MYC, C-JUN, CDC2 AND RB PHOSPHORYLATION, RESEMBLING EVENTS OF EARLY CELL-CYCLE TRAVERSE
CELLS EN-ROUTE TO APOPTOSIS ARE CHARACTERIZED BY THE UP-REGULATION OF C-FOS, C-MYC, C-JUN, CDC2 AND RB PHOSPHORYLATION, RESEMBLING EVENTS OF EARLY CELL-CYCLE TRAVERSE
复制标题
DOI：
10.1002/jcb.240580203
复制
发表时间：
1995-06-01
影响因子：
4
通讯作者：
WANG, E
中科院分区：
文献类型：
--
作者：
PANDEY, S;WANG, E
密度抑制的静态小鼠 Balb/c-3T3 细胞的生存依赖于生长因子。从培养基中取出血清会导致细胞快速死亡，其机制尚不完全清楚。我们研究了血清剥夺对密度抑制的静止瑞士 3T3 细胞的影响，发现它们在完全撤除血清后经历快速细胞死亡。这种细胞死亡的性质与细胞凋亡相似，如细胞和核形态以及 DNA 片段化成寡核小体片段所示。通过研究这一过程中早期细胞周期基因的调节，我们发现在血清剥夺后，当 RE 蛋白的磷酸化形式也出现时，会诱导 c-myc、c-jun、c-fos 和 cdc2 蛋白的存在。这些基因蛋白质产物的上调与 PCNA（一种增殖特异性核抗原）的出现以及 BrdU 的显着掺入相结合，这可能反映了 DNA 修复活性；原位分析表明，BrdU 阳性细胞的 DNA 片段化也呈阳性。这些结果表明，在凋亡过程中，细胞通过表达早期 G(1) 基因经历早期细胞周期遍历的典型事件，甚至可能经历晚期 G(1)/S 期边界，如 PCNA 的存在所示。然而，这些细胞所表现出的穿越细胞周期 G(1) 期的能力似乎是一个失败的事件，因为它们很快就会死亡。 (C) 1995 Wiley-Liss, Inc.
Density-arrested quiescent murine Balb/c-3T3 cells are dependent upon growth factors for their survival. Withdrawal of serum from their medium induces rapid cell death, the mechanism of which is not yet fully understood. We have studied the effect of serum deprivation on density-inhibited quiescent Swiss 3T3 cells and found that they undergo rapid cell death upon total withdrawal of serum. The nature of this cell death is similar to apoptosis, as shown by cellular and nuclear morphology and DNA fragmentation into oligonucleosomal fragments. Investigating the regulation of early cell-cycle genes during this process, we found that c-myc, c-jun, c-fos, and cdc2 protein presence is induced after serum deprivation, when the phosphorylated form of the RE protein also appears. The upregulation of these genes' protein products is coupled with the appearance of PCNA, a proliferation-specific nuclear antigen, as well as significant incorporation of BrdU, which may reflect DNA repair activity; in situ analysis shows that BrdU-positive cells are also positive for DNA fragmentation. These results suggest that en route to apoptosis, cells undergo events typical of early cell-cycle traverse by expressing early G(1) genes and may even experience the late G(1)/S phase boundary, as shown by the presence of PCNA. However, the demonstrated ability of these cells to traverse the G(1) phase of the cell cycle seems to be an abortive event, since they die shortly afterwards. (C) 1995 Wiley-Liss, Inc.