Apollon gene silencing induces apoptosis in breast cancer cells through p53 stabilisation and caspase-3 activation.
Apollon gene silencing induces apoptosis in breast cancer cells through p53 stabilisation and caspase-3 activation.
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DOI：
10.1038/sj.bjc.6604927
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发表时间：
2009-03-10
影响因子：
8.8
通讯作者：
Zaffaroni, N.
中科院分区：
文献类型：
--
作者：
Lopergolo, A.;Pennati, M.;Gandellini, P.;Orlotti, N. I.;Poma, P.;Daidone, M. G.;Folini, M.;Zaffaroni, N.
我们分析了小干扰RNA（siRNA）介导的Apollon沉默的影响，Apollon是凋亡抑制蛋白家族的成员，对人乳腺癌细胞系的增殖潜力和凋亡能力。在野生型p53 ZR75.1细胞中，Apollon敲低导致细胞生长显著的时间依赖性下降和凋亡率增加，这与p53稳定和细胞依赖性凋亡途径的激活有关。细胞与p53特异性siRNA的预孵育导致细胞生长抑制的部分拯救，以及凋亡反应的显著减少，表明p53作为Apollon沉默后细胞生长障碍的主要参与者。Apollon敲低在突变型p53 MDA-MB-231细胞中诱导的抗增殖和促凋亡作用始终不如在ZR 75.1细胞中显著。此外，在Apollon敲低后，caspase-3的活化似乎对于诱导凋亡是必不可少的，因为Apollon特异性siRNA在RNA干扰介导的caspase-3沉默后对caspase-3缺陷的野生型p53 MCF-7细胞或ZR 75.1细胞的存活率没有影响。我们的研究结果表明，p53的稳定和caspase-3的激活一致，以确定Apollon敲低乳腺癌细胞介导的凋亡反应，并建议Apollon是一个潜在的新的治疗靶点，这种恶性肿瘤。
We analysed the effects of small interfering RNA (siRNA)-mediated silencing of Apollon, a member of the inhibitors of apoptosis protein family, on the proliferative potential and ability of human breast cancer cell lines to undergo apoptosis. In wild-type p53 ZR75.1 cells, Apollon knockdown resulted in a marked, time-dependent decline of cell growth and an increased rate of apoptosis, which was associated with p53 stabilisation and activation of the mitochondrial-dependent apoptotic pathway. Pre-incubation of cells with a p53-specific siRNA resulted in a partial rescue of cell growth inhibition, as well as in a marked reduction of the apoptotic response, indicating p53 as a major player in cell growth impairment consequent on Apollon silencing. Apollon knockdown induced consistently less pronounced anti-proliferative and pro-apoptotic effects in mutant p53 MDA-MB-231 cells than in ZR75.1 cells. Furthermore, the activation of caspase-3 seemed to be essential for the induction of apoptosis after Apollon knockdown, as the Apollon-specific siRNA had no effect on the viability of caspase-3-deficient, wild-type p53 MCF-7 cells or the ZR75.1 cells after RNA interference-mediated caspase-3 silencing. Our results indicate that p53 stabilisation and caspase-3 activation concur to determine the apoptotic response mediated by Apollon knockdown in breast cancer cells, and suggest Apollon to be a potential new therapeutic target for this malignancy.
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影响因子：
16
作者：
Bartke, T;Pohl, C;Jentsch, S
通讯作者：
Jentsch, S
DOI：
10.1006/bbrc.1999.1585
发表时间：
1999-11-02
影响因子：
3.1
作者：
Chen, ZH;Naito, M;Tsuruo, T
通讯作者：
Tsuruo, T
影响因子：
5.1
作者：
Chu, L.;Gu, J.;Liu, X.
通讯作者：
Liu, X.
影响因子：
21.3
作者：
Hao, YY;Sekine, K;Naito, M
通讯作者：
Naito, M
影响因子：
64.8
作者：
Dornan, D;Wertz, I;Dixit, VM
通讯作者：
Dixit, VM