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

Tzyh Chyuan Hour, Yan Liang Lai, Ching I. Kuan, Chen Kung Chou, Ju Ming Wang, Huang Yao Tu, Huei Ting Hu, Chang Shen Lin, Wen Jeng Wu, Yeong Shiau Pu, Esta Sterneck, A. Mei Huang

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)325-334
Number of pages10
JournalBiochemical Pharmacology
Volume80
Issue number3
DOIs
Publication statusPublished - 2010 Aug

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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