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 journalArticle

38 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 1

Fingerprint

Cisplatin
Up-Regulation
Cells
Carcinoma
Chemotherapy
CCAAT-Enhancer-Binding Protein-delta
Urinary Bladder
CCAAT-Enhancer-Binding Protein-beta
Drug Therapy
Neoplasms
Tumor Suppressor Genes
Drug Resistance
Urinary Bladder Neoplasms
Transcriptional Activation
Tumors
Reactive Oxygen Species
Therapeutics
Genes
Apoptosis
Cell Line

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Hour, Tzyh Chyuan ; Lai, Yan Liang ; Kuan, Ching I. ; Chou, Chen Kung ; Wang, Ju-Ming ; Tu, Huang Yao ; Hu, Huei Ting ; Lin, Chang Shen ; Wu, Wen Jeng ; Pu, Yeong Shiau ; Sterneck, Esta ; Huang, A. Mei. / Transcriptional up-regulation of SOD1 by CEBPD : A potential target for cisplatin resistant human urothelial carcinoma cells. In: Biochemical Pharmacology. 2010 ; Vol. 80, No. 3. pp. 325-334.
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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.",
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Hour, TC, Lai, YL, Kuan, CI, Chou, CK, Wang, J-M, Tu, HY, Hu, HT, Lin, CS, Wu, WJ, Pu, YS, Sterneck, E & Huang, AM 2010, 'Transcriptional up-regulation of SOD1 by CEBPD: A potential target for cisplatin resistant human urothelial carcinoma cells', Biochemical Pharmacology, vol. 80, no. 3, pp. 325-334. https://doi.org/10.1016/j.bcp.2010.04.007

Transcriptional up-regulation of SOD1 by CEBPD : A potential target for cisplatin resistant human urothelial carcinoma cells. / Hour, Tzyh Chyuan; Lai, Yan Liang; Kuan, Ching I.; Chou, Chen Kung; Wang, Ju-Ming; Tu, Huang Yao; Hu, Huei Ting; Lin, Chang Shen; Wu, Wen Jeng; Pu, Yeong Shiau; Sterneck, Esta; Huang, A. Mei.

In: Biochemical Pharmacology, Vol. 80, No. 3, 01.08.2010, p. 325-334.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Transcriptional up-regulation of SOD1 by CEBPD

T2 - A potential target for cisplatin resistant human urothelial carcinoma cells

AU - Hour, Tzyh Chyuan

AU - Lai, Yan Liang

AU - Kuan, Ching I.

AU - Chou, Chen Kung

AU - Wang, Ju-Ming

AU - Tu, Huang Yao

AU - Hu, Huei Ting

AU - Lin, Chang Shen

AU - Wu, Wen Jeng

AU - Pu, Yeong Shiau

AU - Sterneck, Esta

AU - Huang, A. Mei

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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.

AB - 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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