Up-regulation of Bfl-1/A1 via NF-κB activation in cisplatin-resistant human bladder cancer cell line
Up-regulation of Bfl-1/A1 via NF-κB activation in cisplatin-resistant human bladder cancer cell line
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DOI：
10.1016/j.canlet.2004.02.021
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发表时间：
2004-08-20
期刊：
影响因子：
9.7
通讯作者：
Lee, HG
中科院分区：
文献类型：
--
作者：
Kim, JK;Kim, KD;Lee, HG
顺式二胺二氯铂（II）（顺铂）是目前用于治疗膀胱癌的有效抗癌药物。然而，由于出现顺铂耐药膀胱肿瘤细胞，该药的长期临床应用往往受到限制。我们采用差异显示逆转录酶聚合酶链反应的方法鉴定亲本人类膀胱癌细胞株T24和3个顺铂耐药细胞株的差异表达基因。我们在此报道顺铂耐药细胞系与亲本细胞相比，在胎儿肝(Bfl-1)/A1中过度表达Bcl-2家族蛋白Bcl-2相关基因。顺铂和γ辐照诱导Bfl-1/A1在T24R2细胞中表达，而在T24细胞中不表达。Bcl-2家族成员中，bcl -1/A1在耐药细胞中的表达水平变化最为显著。在T24R2细胞中，顺铂和γ辐射选择性地使核因子- kappab （NF-kappaB）发生核易位。在T24R2细胞中，顺铂也能阻止线粒体去极化和细胞死亡。此外，Bfl-1/A1抑制顺铂和tnf α诱导的BOSC23细胞凋亡。我们的研究结果表明，NF-kappaB诱导Bfl-1/A1可能在控制膀胱肿瘤细胞对顺铂反应的耐药中起重要作用。2004爱思唯尔爱尔兰有限公司版权所有。
The potent anti-cancer agent cis-diamminedichloroplatinum (II) (cisplatin) is currently used for treating bladder cancer. However, clinical use of this drug for long periods is often limited because of the appearance of cisplatin-resistant bladder tumor cells. We employed the method of a differential display reverse transcriptase polymerase chain reaction to identify the differentially expressed genes in the parental human bladder cancer cell line, T24 and three cisplatin-resistant cell lines. We report here that cisplatin-resistant cell lines overexpress Bcl-2 family protein Bcl-2-related gene expressed in fetal liver (Bfl-1)/A1 as compared with their parental cell. Cisplatin and gamma-irradiation induced expression of Bfl-1/A1 in T24R2 cells but not in T24 cells. Among Bcl-2 family members, Bfl-1/A1 showed the most significant alteration of the expression level in resistant cells. The nuclear translocation of nuclear factor-kappaB (NF-kappaB) by cisplatin and gamma-irradiation selectively occurred in T24R2 cells. Mitochondrial depolarization and cell death by cisplatin were also prevented in T24R2 cells. Moreover, Bfl-1/A1 inhibited cisplatin- and TNF-alpha-induced apoptosis in BOSC23 cells. Our findings suggest that the induction of Bfl-1/A1 by NF-kappaB may be important in controlling resistance to cisplatin responses in bladder tumor cells. (C) 2004 Elsevier Ireland Ltd. All rights reserved.