Transcriptional up-regulation of SOD1 by CEBPD: a potential target for cisplatin resistant human urothelial carcinoma cells.
Transcriptional up-regulation of SOD1 by CEBPD: a potential target for cisplatin resistant human urothelial carcinoma cells.
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DOI：
10.1016/j.bcp.2010.04.007
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发表时间：
2010-08-01
影响因子：
5.8
通讯作者：
Huang AM
中科院分区：
文献类型：
--
作者：
Hour TC;Lai YL;Kuan CI;Chou CK;Wang JM;Tu HY;Hu HT;Lin CS;Wu WJ;Pu YS;Sterneck E;Huang AM
膀胱癌是美国男性第四常见的癌症类型（女性第九）。顺铂是一种有效的药物对最常见的亚型，尿路上皮癌。然而，化疗耐药性的发展是成功治疗这种癌症和其他癌症的严重临床问题。更好地了解顺铂治疗反应的细胞和分子事件以及耐药的发展对于改善患者的治疗选择至关重要。在这里，我们报告了CCAAT/增强子结合蛋白δ（CEBPD，C/EBPδ，NF-IL 6 β）的表达在人膀胱尿路上皮癌NTUB 1细胞系中由顺铂诱导，并且在顺铂耐药亚系中特异性升高。CEBPD的表达通过直接启动子反式激活诱导Cu/Zn-超氧化物歧化酶（SOD 1）的表达来减少顺铂诱导的NTUB 1细胞中的活性氧（ROS）和凋亡。一些报道暗示CEBPD是肿瘤抑制基因。这项研究揭示了CEBPD在赋予耐药性方面的新作用，表明它也可以是促癌的。此外，我们的数据表明，SOD抑制剂，这已经被用作抗血管生成剂，可能是适合的组合化疗，以预防或治疗顺铂耐药的膀胱癌和可能的其他癌症。
Bladder cancer is the fourth most common type of cancer in men (ninth in women) in the United States. Cisplatin is an effective agent against the most common subtype, urothelial carcinoma. However, the development of chemotherapy resistance is a severe clinical problem for the successful treatment of this and other cancers. A better understanding of the cellular and molecular events in response to cisplatin treatment and the development of resistance are critical to improve the therapeutic options for patients. Here, we report that expression of the CCAAT/enhancer binding protein delta (CEBPD, C/EBPδ, NF-IL6β) is induced by cisplatin in the human bladder urothelial carcinoma NTUB1 cell line and is specifically elevated in a cisplatin resistant subline. Expression of CEBPD reduced cisplatin-induced reactive oxygen species (ROS) and apoptosis in NTUB1 cells by inducing the expression of Cu/Zn-superoxide dismutase (SOD1) via direct promoter transactivation. Several reports have implicated CEBPD as a tumor suppressor gene. This study reveals a novel role for CEBPD in conferring drug resistance, suggesting that it can also be pro-oncogenic. Furthermore, our data suggest that SOD inhibitors, which are already used as anti-angiogenic agents, may be suitable for combinatorial chemotherapy to prevent or treat cisplatin resistance in bladder and possibly other cancers.
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影响因子：
3.1
作者：
Lowndes, Sarah A.;Sheldon, Helen V.;Harris, Adrian L.
通讯作者：
Harris, Adrian L.
影响因子：
50.5
作者：
Kaufman, D. S.
通讯作者：
Kaufman, D. S.
影响因子：
14.9
作者：
Heinemeyer, T;Wingender, E;Kolchanov, NA
通讯作者：
Kolchanov, NA
影响因子：
4
作者：
Johnson, PF
通讯作者：
Johnson, PF
影响因子：
2.4
作者：
Matsumoto, H;Wada, T;Naito, K
通讯作者：
Naito, K