p53-independent apoptosis and p53-dependent block of DNA rereplication following mitotic spindle inhibition in human cells
p53-independent apoptosis and p53-dependent block of DNA rereplication following mitotic spindle inhibition in human cells
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DOI：
10.1006/excr.1999.4554
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发表时间：
1999-08-01
影响因子：
3.7
通讯作者：
Cundari, E
中科院分区：
文献类型：
--
作者：
Casenghi, M;Mangiacasale, R;Cundari, E
我们研究了人类转化细胞对有丝分裂纺锤体抑制的反应。两对细胞系，K562 及其抗细小病毒的 KS 衍生克隆，分别不表达和表达 p53，持续暴露于诺考达唑。在两个细胞系中均观察到细胞凋亡，表明有丝分裂纺锤体损伤诱导了不依赖于 p53 的细胞凋亡。通过流式细胞术测定 MPM2 抗原和细胞周期蛋白 B1 表达，结合姐妹着丝粒分离的细胞遗传学分析，表明在短暂的有丝分裂延迟后，两个细胞系都退出有丝分裂。两种细胞系都退出有丝分裂而没有染色单体分离。 K562 p53缺陷细胞进一步恢复DNA合成，产生DNA含量高于4C的细胞，并重新进入多倍体循环。相比之下，KS 细胞随后在四倍体状态下经历了 G1 期停滞。因此，四倍体细胞中的 G1 停滞需要再复制检查点中的 p53 功能，以防止异常有丝分裂后的 G1/S 转变；相反，在没有有丝分裂纺锤体的情况下，p53 表达对于触发细胞凋亡反应是可有可无的。 (C) 1999 年学术出版社。
We have studied the response of human transformed cells to mitotic spindle inhibition. Two paired cell lines, K562 and its parvovirus-resistant KS derivative clone, respectively nonexpressing and expressing p53, were continuously exposed to nocodazole. Apoptotic cells were observed in both lines, indicating that mitotic spindle impairment induced p53-independent apoptosis, After a transient mitotic delay, both cell lines exited mitosis, as revealed by flow-cytometric determination of MPM2 antigen and cyclin B1 expression, coupled to cytogenetic analysis of sister centromere separation. Both cell lines exited mitosis without chromatid segregation. K562 p53-deficient cells further resumed DNA synthesis, giving rise to cells with a DNA content above 4C, and reentered a polyploid cycle. In contrast, KS cells underwent a subsequent G1 arrest in the tetraploid state. Thus, G1 arrest in tetraploid cells requires p53 function in the rereplication check-point which prevents the G1/S transition following aberrant mitosis; in contrast, p53 expression is dispensable for triggering the apoptotic response in the absence of mitotic spindle. (C) 1999 Academic Press.