Up-regulation of Bfl-1/A1 via NF-κB activation in cisplatin-resistant human bladder cancer cell line

Jin Koo Kim, Kwang Dong Kim, Eunsik Lee, Jong Seok Lim, Hee Jun Cho, Hyun Kyung Yoon, Mi Young Cho, Kyoung Eun Baek, Yuk Pheel Park, Sang Gi Paik, Yong Kyung Choe, Hee Gu Lee

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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 γ-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-κB) by cisplatin and γ-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-α-induced apoptosis in BOSC23 cells. Our findings suggest that the induction of Bfl-1/A1 by NF-κB may be important in controlling resistance to cisplatin responses in bladder tumor cells.

Original languageEnglish (US)
Pages (from-to)61-70
Number of pages10
JournalCancer Letters
Volume212
Issue number1
DOIs
StatePublished - Aug 20 2004
Externally publishedYes

Keywords

  • Bfl-1, Bcl-2-related gene expressed in fetal liver
  • Bfl-1/A1
  • Cisplatin, cis-diamminedichloroplatinum (II)
  • Cisplatin-resistant bladder cancer
  • Differential display
  • NF-κB

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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