53BP1 suppresses tumor growth and promotes susceptibility to apoptosis of ovarian cancer cells through modulation of the Akt pathway.
53BP1 suppresses tumor growth and promotes susceptibility to apoptosis of ovarian cancer cells through modulation of the Akt pathway.
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53BP1 通过调节 Akt 通路抑制肿瘤生长并促进卵巢癌细胞凋亡
DOI：
10.3892/or.2012.1641
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发表时间：
2012-04
期刊：
影响因子：
4.2
通讯作者：
Kong B
中科院分区：
文献类型：
--
作者：
Hong S;Li X;Zhao Y;Yang Q;Kong B
53BP1作为DNA损伤反应的关键成分已被广泛研究，但对53BP1在预防肿瘤发展中的作用知之甚少。本研究旨在探讨53BP1基因表达修饰对卵巢癌细胞生物学行为的影响，并阐明53BP1在癌细胞中启动的细胞通路(S)。利用DNA脂质体技术分别上调和下调53BP1在A2780和HO-8910 PM细胞中的表达。检测细胞存活率、克隆形成能力和细胞周期变化。用流式细胞仪分析细胞凋亡率。免疫印迹法检测细胞凋亡和细胞信号转导相关蛋白的表达。53BP1的高表达降低了细胞的存活率和克隆形成能力，并诱导细胞发生G2/M期停滞和凋亡。Bax、P21、caspase-3蛋白表达上调，而Bcl2、p-Akt表达降低，差异有统计学意义。相反，53BP1的解除调控显著提高了细胞的增殖能力。总体而言，我们的数据表明53BP1参与了控制细胞增殖和生长以及防止肿瘤发展的几个重要步骤。
53BP1 has been extensively studied as a key component of the DNA damage response, but little is known regarding the role of 53BP1 in preventing tumor development. The present study was designed to assess the impact of the modification of 53BP1 gene expression on the biological behavior of ovarian cancer cell lines and to elucidate the cellular pathway(s) triggered by 53BP1 in cancer cells. DNA liposome transfection technology was employed to increase and to knock down the expression of 53BP1 in A2780 and HO-8910PM cells, respectively. Viability, clonogenicity and cell cycle profiles were evaluated. Cell apoptosis was analyzed using flow cytometric assay. The expression of proteins related to apoptosis and cell signal transduction was assessed using western blotting. Increased expression of 53BP1 decreased the viability and the clonogenicity, and induced G2/M arrest and apoptosis of the treated cells. The protein expression of Bax, P21 and caspase-3 was upregulated, while the levels of Bcl-2 and p-Akt were reduced to a statistically significant level. In contrast, deregulation of 53BP1 significantly increased proliferative ability. Collectively, our data suggest that 53BP1 is involved in several important steps in controlling cell proliferation and growth and preventing tumor development.
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影响因子：
4.7
作者：
Nuciforo, Paolo Giovanni;Luise, Chiara;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
DOI：
10.1016/j.bbrc.2009.01.097
发表时间：
2009-03-06
影响因子：
3.1
作者：
Kucharzewska, Paulina;Welch, Johanna E.;Belting, Mattias
通讯作者：
Belting, Mattias
影响因子：
6.1
作者：
Wright, Jay W.;Pejovic, Tanja;Stouffer, Richard L.
通讯作者：
Stouffer, Richard L.
DOI：
10.1073/pnas.1004522107
发表时间：
2010-11-16
影响因子：
11.1
作者：
Miao, Benchun;Skidan, Igor;Degterev, Alexei
通讯作者：
Degterev, Alexei
影响因子：
5.2
作者：
Wu, Ping-Ping;Chung, Hui-Wen;Chung, Jing-Gung
通讯作者：
Chung, Jing-Gung