Cell cycle-independent regulation of p21Waf1/Cip1 and retinoblastoma protein during okadaic acid-induced apoptosis is coupled with induction of Bax protein in human breast carcinoma cells.
Cell cycle-independent regulation of p21Waf1/Cip1 and retinoblastoma protein during okadaic acid-induced apoptosis is coupled with induction of Bax protein in human breast carcinoma cells.
复制标题
在冈田酸诱导的细胞凋亡过程中，p21Waf1/Cip1 和视网膜母细胞瘤蛋白的细胞周期独立调节与人乳腺癌细胞中 Bax 蛋白的诱导相结合。
DOI：
--
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
A. Fornace
中科院分区：
文献类型：
--
作者：
M. Sheikh;M. García;Q. Zhan;Y. Liu;A. Fornace
冈田酸（OA）是一种丝氨酸/苏氨酸蛋白磷酸酶抑制剂，并且已显示在许多不同的肿瘤细胞系（包括人乳腺癌（HBC）细胞）中诱导凋亡。OA诱导细胞凋亡的分子基础仍有待研究。在这里，我们证明，OA浓度，抑制蛋白磷酸酶1和2A是足以诱导HBC细胞凋亡。在MCF-7细胞中，OA诱导的凋亡与内源性p53、p21 Waf 1/Cip 1和Bax蛋白的过表达相结合，而Rb蛋白水平降低。OA还诱导细胞凋亡，并伴随着提高p21 Waf 1/Cip 1和Bex水平的人乳头瘤病毒蛋白E6转染的MCF-7细胞的变体，其中p53功能已被破坏。相比之下，OA对野生型E6转染的MCF-7细胞中Gadd 45和Bcl 2蛋白的水平或亚细胞定位没有影响。在两种细胞类型中，Bcl-xL、Bcl-xS和巴克水平在OA处理后也没有变化。OA诱导的细胞凋亡及其对上述分子标志物表达的影响发生在细胞周期时相分布没有任何可检测到的变化的情况下。根据我们的研究结果，我们得出以下结论：（a）OA诱导的HBC细胞凋亡的发生独立于细胞周期阻滞;（B）野生型p53功能不是OA诱导的细胞死亡的绝对先决条件;（c）OA诱导的细胞凋亡与内源性p21 Waf 1/Cip 1和Bax蛋白水平的上调有关。
Okadaic acid (OA) is a serine/threonine protein phosphatase inhibitor and has been shown to induce apoptosis in a number of different tumor cell lines, including human breast carcinoma (HBC) cells. The molecular basis of OA-induced apoptosis remains to be investigated. Here, we demonstrate that the OA concentration that inhibits only protein phosphatase 1 and 2A was sufficient to induce apoptosis in HBC cells. In MCF-7 cells, the OA-induced apoptosis was coupled with the overexpression of endogenous p53, p21Waf1/Cip1, and Bax proteins, whereas the Rb protein levels were decreased. OA also induced apoptosis and concomitantly enhanced the p21Waf1/Cip1 and Bex levels in human papilloma virus protein E6-transfected variants of MCF-7 cells, in which p53 function had been disrupted. OA, by contrast, had no effect on the levels or the subcellular localization of Gadd45 and Bcl2 proteins in either wild-type of E6-transfected MCF-7 cells. Bcl-xL, Bcl-xS, and Bak levels were also unchanged after OA treatment in both cell types. OA-induced apoptosis and its effect on the expression of the above molecular markers occurred in the absence of any detectable changes in the cell cycle phase distribution. On the basis of our findings, we conclude the following: (a) OA-induced apoptosis in HBC cells occurs independently of cell cycle arrest; (b) the wild-type p53 function is not an absolute prerequisite for OA-induced cell death; and (c) OA-induced apoptosis is associated with up-regulation of endogenous p21Waf1/Cip1 and Bax protein levels.
登录
查看更多内容
影响因子：
8
作者：
Qimin Zhan;Sajan Fan;Insoo Bae;C. Guillouf;D. Liebermann;Patrick M. O'Connor;A. Fornace
通讯作者：
Qimin Zhan;Sajan Fan;Insoo Bae;C. Guillouf;D. Liebermann;Patrick M. O'Connor;A. Fornace
影响因子：
10.5
作者：
CANMAN, CE;GILMER, TM;KASTAN, MB
通讯作者：
KASTAN, MB
影响因子：
1.7
作者：
Schulkens, Iris A.;Castricum, Kitty C. M.;Thijssen, Victor L.
通讯作者：
Thijssen, Victor L.
影响因子：
11.4
作者：
CHITTENDEN, T;FLEMINGTON, C;LUTZ, RJ
通讯作者：
LUTZ, RJ