Dual induction of caspase 3- and transglutaminase-dependent apoptosis by acyclic retinoid in hepatocellular carcinoma cells.
Dual induction of caspase 3- and transglutaminase-dependent apoptosis by acyclic retinoid in hepatocellular carcinoma cells.
复制标题
DOI：
10.1186/1476-4598-10-4
复制
发表时间：
2011-01-09
期刊：
影响因子：
37.3
通讯作者：
Kojima S
中科院分区：
文献类型：
--
作者：
Tatsukawa H;Sano T;Fukaya Y;Ishibashi N;Watanabe M;Okuno M;Moriwaki H;Kojima S
肝细胞癌因其复发率高而死亡率高。去环维A酸类化合物通过诱导肝细胞癌细胞的凋亡来预防手术切除原发肿瘤患者的肝细胞癌复发，尽管其分子机制尚不清楚。用去环维A酸类化合物处理培养的人肝癌细胞、裸鼠移植肝癌细胞和给予N-二乙基亚硝胺的大鼠。检测活化的半胱氨酸天冬氨酸氨基转移酶3(Caspase 3)和谷氨酰胺转氨酶2(TG2)水平、Sp1交联物及其活性、表皮生长因子受体表达和细胞凋亡率的变化。去环维A酸类化合物同时刺激caspase3的激活，TG2的表达、核定位和交联化活性，导致转录因子Sp1的交联和失活，从而减少3种肝癌细胞系的表皮生长因子受体的表达和细胞死亡。这些作用可通过caspase抑制剂、反义TG2的转染、功能Sp1的恢复或过量的表皮生长因子来部分恢复。在N-二乙基亚硝胺诱导的大鼠肝癌模型中，经去环维A酸处理后，移植于裸鼠体内的肝癌细胞和肝内癌区均有TG2和交联型Sp1的核表达，caspase3也被激活。去环维A酸类药物通过修饰和失活Sp1双重激活caspase3和TG2诱导肝癌细胞凋亡，导致表皮生长因子受体表达减少。
Hepatocellular carcinoma has a high mortality rate due to its rate of recurrence. Acyclic retinoid prevents recurrence of hepatocellular carcinoma in patients after surgical removal of their primary tumors by inducing apoptosis in hepatocellular carcinoma cells, although the molecular mechanisms of action are not understood. Human hepatocellular carcinoma cells in culture, as well as nude mice transplanted with hepatocellular carcinoma cells and rats given with N-diethylnitrosamine were treated with acyclic retinoid. Changes in activated caspase 3 and transglutaminase 2 (TG2) levels, Sp1 cross-linking and its activities, expression of epidermal growth factor receptor, and apoptotic levels were measured. Acyclic retinoid simultaneously stimulated the activation of caspase 3, and the expression, nuclear localization and crosslinking activity of TG2, resulting in crosslinking and inactivation of the transcription factor, Sp1, thereby reducing expression of epidermal growth factor receptor and cell death in three hepatocellular carcinoma cell lines. These effects were partially restored by a caspase inhibitor, transfection of antisense TG2, restoration of functional Sp1, or an excess of epidermal growth factor. Nuclear expression of TG2 and crosslinked Sp1, as also activated caspase 3 were found in both hepatocellular carcinoma cells transplanted into nude mice and cancerous regions within the liver in N-diethylnitrosamine-induced hepatocarcinogenesis model in rats, following treatment of animals with acyclic retinoid. Treatment with acyclic retinoid produces a dual activation of caspase 3 and TG2 induced apoptosis of hepatocellular carcinoma cells via modification and inactivation of Sp1, resulting in reduced expression of epidermal growth factor receptor.
登录
查看更多内容
影响因子：
3.5
作者：
Peng, XJ;Zhang, YH;Lokshin, A
通讯作者：
Lokshin, A
影响因子：
29.4
作者：
Shao, RX;Otsuka, M;Omata, M
通讯作者：
Omata, M
影响因子：
11.5
作者：
Shimizu, M;Suzui, M;Weinstein, IB
通讯作者：
Weinstein, IB
影响因子：
12.4
作者：
Fabbi, M;Marimpietri, D;Cosulich, E
通讯作者：
Cosulich, E
DOI：
10.1006/bbrc.1996.0188
发表时间：
1996-02-06
影响因子：
3.1
作者：
Nakamura, N;Shidoji, Y;Muto, Y
通讯作者：
Muto, Y