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Transcriptional up-regulation of SOD1 by CEBPD: A potential target for cisplatin resistant human urothelial carcinoma cells

  1. Author:
    Hour, T. C.
    Lai, Y. L.
    Kuan, C. I.
    Chou, C. K.
    Wang, J. M.
    Tu, H. Y.
    Hu, H. T.
    Lin, C. S.
    Wu, W. J.
    Pu, Y. S.
    Sterneck, E.
    Huang, A. M.

  2. Author Address

    [Hour, Tzyh-Chyuan; Lai, Yan-Liang; Kuan, Ching-I; Hu, Huei-Ting; Huang, A-Mei] Kaohsiung Med Univ, Dept Med, Grad Inst Biochem, Kaohsiung 807, Taiwan. [Hour, Tzyh-Chyuan; Huang, A-Mei] Kaohsiung Med Univ, Ctr Excellence Environm Med, Kaohsiung 807, Taiwan. [Chou, Chen-Kung] Chang Gung Univ, Dept Biomed Sci, Tao Yuan, Taiwan. [Wang, Ju-Ming] Natl Cheng Kung Univ, Inst Biosignal Transduct, Tainan 70101, Taiwan. [Tu, Huang-Yao] Kaohsiung Med Univ, Dept Pharm, Coll Pharm, Kaohsiung 807, Taiwan. [Lin, Chang-Shen] Kaohsiung Med Univ, Dept Med, Grad Inst Med, Kaohsiung 807, Taiwan. [Wu, Wen-Jeng] Kaohsiung Med Univ, Dept Urol, Kaohsiung Med Univ Hosp, Kaohsiung 807, Taiwan. [Pu, Yeong-Shiau] Natl Taiwan Univ Hosp, Dept Urol, Taipei, Taiwan. [Sterneck, Esta] NCI, Ctr Canc Res, Frederick, MD 21702 USA.;Huang, AM, Kaohsiung Med Univ, Dept Med, Grad Inst Biochem, 100 Shi Chuan 1st Rd, Kaohsiung 807, Taiwan.;amhuang@kmu.edu.tw
    1. Year: 2010
    2. Date: Aug
  2. Journal: Biochemical Pharmacology
    1. 80
    2. 3
    3. Pages: 325-334
  4. Type of Article: Article
  5. ISSN: 0006-2952
  1. Abstract:

    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 impreve the therapeutic options for patients. Here, we report that expression of the CCAAT/enhancer binding protein delta (CEBPD, C/EBP delta, NE-IL6 beta) 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. (C) 2010 Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.bcp.2010.04.007
  3. View record in Web of Science®
  4. WOS: 000278712100005

Library Notes

  1. Fiscal Year: FY2009-2010
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